The capacity of cells to alter bioenergetics in response to the demands of various biological processes is essential for normal physiology. The coordination of energy sensing and production with highly energy-demanding cellular processes, such as cell division, is poorly understood. Here, we show that a cell cycle-dependent mitochondrial Ca2+ transient connects energy sensing to mitochondrial activity for mitotic progression. The mitochondrial Ca2+ uniporter (MCU) mediates a rapid mitochondrial Ca2+ transient during mitosis. Inhibition of mitochondrial Ca2+ transients via MCU depletion causes spindle checkpoint-dependent mitotic delay. Cellular ATP levels drop during early mitosis, and the mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis. This is achieved through mitosis-specific MCU phosphorylation and activation by the mitochondrial translocation of energy sensor AMP-activated protein kinase (AMPK). Our results establish a critical role for AMPK- and MCU-dependent mitochondrial Ca2+ signalling in mitosis and reveal a mechanism of mitochondrial metabolic adaptation to acute cellular energy stress.
This is a preview of subscription content
Subscribe to Nature+
Get immediate online access to the entire Nature family of 50+ journals
Subscribe to Journal
Get full journal access for 1 year
only $8.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Lee, I. H. & Finkel, T. Metabolic regulation of the cell cycle. Curr. Opin. Cell Biol. 25, 724–729 (2013).
Buchakjian, M. R. & Kornbluth, S. The engine driving the ship: metabolic steering of cell proliferation and death. Nat. Rev. Mol. Cell Biol. 11, 715–727 (2010).
Salazar-Roa, M. & Malumbres, M. Fueling the cell division cycle. Trends Cell Biol. 27, 69–81 (2017).
Almeida, A., Bolanos, J. P. & Moncada, S. E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation. Proc. Natl Acad. Sci. USA 107, 738–741 (2010).
Harbauer, A. B. et al. Mitochondria. Cell cycle-dependent regulation of mitochondrial preprotein translocase. Science 346, 1109–1113 (2014).
Jones, R. G. et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell 18, 283–293 (2005).
Mandal, S., Guptan, P., Owusu-Ansah, E. & Banerjee, U. Mitochondrial regulation of cell cycle progression during development as revealed by the tenured mutation in Drosophila. Dev. Cell 9, 843–854 (2005).
Lee, I. H. et al. Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science 336, 225–228 (2012).
DiGregorio, P. J., Ubersax, J. A. & O’Farrell, P. H. Hypoxia and nitric oxide induce a rapid, reversible cell cycle arrest of the Drosophila syncytial divisions. J. Biol. Chem. 276, 1930–1937 (2001).
Hardie, D. G., Ross, F. A. & Hawley, S. A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 13, 251–262 (2012).
Banko, M. R. et al. Chemical genetic screen for AMPKalpha2 substrates uncovers a network of proteins involved in mitosis. Mol. Cell 44, 878–892 (2011).
Vazquez-Martin, A., Oliveras-Ferraros, C. & Menendez, J. A. The active form of the metabolic sensor: AMP-activated protein kinase (AMPK) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis. Cell Cycle 8, 2385–2398 (2009).
Domenech, E. et al. AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest. Nat. Cell Biol. 17, 1304–1316 (2015).
Poenie, M., Alderton, J., Steinhardt, R. & Tsien, R. Calcium rises abruptly and briefly throughout the cell at the onset of anaphase. Science 233, 886–889 (1986).
Ratan, R. R., Maxfield, F. R. & Shelanski, M. L. Long-lasting and rapid calcium changes during mitosis. J. Cell Biol. 107, 993–999 (1988).
Poenie, M., Alderton, J., Tsien, R. Y. & Steinhardt, R. A. Changes of free calcium levels with stages of the cell division cycle. Nature 315, 147–149 (1985).
Izant, J. G. The role of calcium ions during mitosis. Calcium participates in the anaphase trigger. Chromosoma 88, 1–10 (1983).
Tombes, R. M. & Borisy, G. G. Intracellular free calcium and mitosis in mammalian cells: anaphase onset is calcium modulated, but is not triggered by a brief transient. J. Cell Biol. 109, 627–636 (1989).
Lorca, T. et al. Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. Nature 366, 270–273 (1993).
Rauh, N. R., Schmidt, A., Bormann, J., Nigg, E. A. & Mayer, T. U. Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation. Nature 437, 1048–1052 (2005).
Finkel, T. et al. The ins and outs of mitochondrial calcium. Circ. Res. 116, 1810–1819 (2015).
Kamer, K. J. & Mootha, V. K. The molecular era of the mitochondrial calcium uniporter. Nat. Rev. Mol. Cell Biol. 16, 545–553 (2015).
De Stefani, D., Rizzuto, R. & Pozzan, T. Enjoy the trip: calcium in mitochondria back and forth. Annu. Rev. Biochem. 85, 161–192 (2016).
De Stefani, D., Raffaello, A., Teardo, E., Szabo, I. & Rizzuto, R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476, 336–340 (2011).
Baughman, J. M. et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476, 341–345 (2011).
Chaudhuri, D., Sancak, Y., Mootha, V. K. & Clapham, D. E. MCU encodes the pore conducting mitochondrial calcium currents. eLife 2, e00704 (2013).
Mammucari, C. et al. Mitochondrial calcium uptake in organ physiology: from molecular mechanism to animal models. Pflugers Archiv. 470, 1165–1179 (2018).
Mammucari, C. et al. The mitochondrial calcium uniporter controls skeletal muscle trophism in vivo. Cell Rep. 10, 1269–1279 (2015).
Pan, X. et al. The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. Nat. Cell Biol. 15, 1464–1472 (2013).
Tosatto, A. et al. The mitochondrial calcium uniporter regulates breast cancer progression via HIF-1α. EMBO Mol. Med. 8, 569–585 (2016).
Chen, T. W. et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).
Etemad, B. & Kops, G. J. Attachment issues: kinetochore transformations and spindle checkpoint silencing. Curr. Opin. Cell Biol. 39, 101–108 (2016).
London, N. & Biggins, S. Signalling dynamics in the spindle checkpoint response. Nat. Rev. Mol. Cell Biol. 15, 736–747 (2014).
Cardenas, C. et al. Selective vulnerability of cancer cells by inhibition of Ca2+ transfer from endoplasmic reticulum to mitochondria. Cell Rep. 14, 2313–2324 (2016).
Murphy, E. et al. Unresolved questions from the analysis of mice lacking MCU expression. Biochem. Biophys. Res. Commun. 449, 384–385 (2014).
Montemurro, C. et al. Cell cycle-related metabolism and mitochondrial dynamics in a replication-competent pancreatic beta-cell line. Cell Cycle 16, 2086–2099 (2017).
Wang, Z. et al. Cyclin B1/Cdk1 coordinates mitochondrial respiration for cell-cycle G2/M progression. Dev. Cell 29, 217–232 (2014).
Qian, Y. et al. Extracellular ATP is internalized by macropinocytosis and induces intracellular ATP increase and drug resistance in cancer cells. Cancer Lett. 351, 242–251 (2014).
Nakada, D., Saunders, T. L. & Morrison, S. J. Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature 468, 653–658 (2010).
Nogales, E. & Ramey, V. H. Structure–function insights into the yeast Dam1 kinetochore complex. J. Cell Sci. 122, 3831–3836 (2009).
Desai, A., Verma, S., Mitchison, T. J. & Walczak, C. E. Kin I kinesins are microtubule-destabilizing enzymes. Cell 96, 69–78 (1999).
Hartman, J. J. & Vale, R. D. Microtubule disassembly by ATP-dependent oligomerization of the AAA enzyme katanin. Science 286, 782–785 (1999).
Bershadsky, A. D. & Gelfand, V. I. ATP-dependent regulation of cytoplasmic microtubule disassembly. Proc. Natl Acad. Sci. USA 78, 3610–3613 (1981).
Koshland, D. E., Mitchison, T. J. & Kirschner, M. W. Polewards chromosome movement driven by microtubule depolymerization in vitro. Nature 331, 499–504 (1988).
Chaudry, I. H. & Gould, M. K. Evidence for the uptake of ATP by rat soleus muscle in vitro. Biochim. Biophys. Acta 196, 320–326 (1970).
Kolassa, N. & Pfleger, K. Adenosine uptake by erythrocytes of man, rat and guinea-pig and its inhibition by hexobendine and dipyridamole. Biochem. Pharmacol. 24, 154–156 (1975).
Joiner, M. L. et al. CaMKII determines mitochondrial stress responses in heart. Nature 491, 269–273 (2012).
Zhang, Y. et al. Metformin interacts with AMPK through binding to gamma subunit. Mol. Cell. Biochem. 368, 69–76 (2012).
Toyama, E. Q. et al. Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science 351, 275–281 (2016).
Moreau, B., Nelson, C. & Parekh, A. B. Biphasic regulation of mitochondrial Ca2+ uptake by cytosolic Ca2+ concentration. Curr. Biol. 16, 1672–1677 (2006).
Herzig, S. & Shaw, R. J. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat. Rev. Mol. Cell Biol. 19, 121–135 (2018).
Abu-Elheiga, L. et al. The subcellular localization of acetyl-CoA carboxylase 2. Proc. Natl Acad. Sci. USA 97, 1444–1449 (2000).
Watanabe, S. et al. Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis. Cell Rep. 5, 926–932 (2013).
Akerboom, J. et al. Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics. Front. Mol. Neurosci. 6, 2 (2013).
Bermejo, C., Haerizadeh, F., Takanaga, H., Chermak, D. & Frommer, W. B. Dynamic analysis of cytosolic glucose and ATP levels in yeast using optical sensors. Biochem. J. 432, 399–406 (2010).
Imamura, H. et al. Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators. Proc. Natl Acad. Sci. USA 106, 15651–15656 (2009).
Wang, L. et al. Structural and mechanistic insights into MICU1 regulation of mitochondrial calcium uptake. EMBO J. 33, 594–604 (2014).
Dong, Z. et al. Mitochondrial Ca2+ uniporter is a mitochondrial luminal redox sensor that augments MCU channel activity. Mol. Cell 65, 1014–1028 (2017).
Fang, L., Seki, A. & Fang, G. SKAP associates with kinetochores and promotes the metaphase-to-anaphase transition. Cell Cycle 8, 2819–2827 (2009).
Gao, Y. F. et al. Cdk1-phosphorylated CUEDC2 promotes spindle checkpoint inactivation and chromosomal instability. Nat. Cell Biol. 13, 924–933 (2011).
Li, T. et al. SUMOylated NKAP is essential for chromosome alignment by anchoring CENP-E to kinetochores. Nat. Commun. 7, 12969 (2016).
The authors thank Y.X. Zheng, H.T. Yu and Z.G. Liu for discussions and critical reading of the manuscript. They also thank D.D. Stefani for providing 4mt-GCaMP6 plasmids, Y.Q. Shen for the mtAequorin plasmid, and K. Wang and X. Xu for assistance with microscopy assays. This work was supported by the National Natural Science Foundation of China (grant numbers 81522034, 31570840, 81521064, 31571419, 31370915 and 81790252), the China National Basic Research Program (2014CB910603), the International S&T Cooperation Program of China (2015DFA31610), Beijing Nova Program (Z151100000315085, Z161100004916166), Beijing Talents Foundation (2016000021223ZK24), National Key Research and Development Program (2017YFC1601100) and a NIH grant (R01HL142589).
The authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Integrated supplementary information
Mitochondrial Ca2+ transients in cell cycle. a, Representative images of HeLa cells expressing mitochondrial Ca2+ probe 4mt-GCaMP6 (Green, left panel) co-stained with MitoTracker Red (middle panel). The merged image is shown in the right panel. b, Representative image of HeLa/RFP-H2B cells expressing 4mt-GCaMP6. White arrows indicate mitotic cells. Some of the mitotic cells exhibit higher mitochondrial Ca2+ levels. c, Selected frames of a mitochondrial Ca2+ transient during mitosis in HeLa/RFP-H2B cell expressing 4mt-GCaMP6. The cells were synchronized by a thymidine block and released to fresh medium without CGP37157. The mitotic progression was then imaged by fluorescence time-lapse microscopy. The time on the images is in minute. See Supplementary Video 1. d, Mitochondrial Ca2+ levels in HeLa cells pretreated with DMSO or 5 μM CGP37157 were measured by fluorescence of 4mt-GCaMP6 following 100 μM histamine stimulation. n = 25 cells for each condition. e, HeLa cells pretreated with DMSO or 5 μM CGP37157 were analyzed for the lengths of time from NEB to anaphase onset based on time-lapse imaging. n = 57 DMSO-pretreated cells and 47 CGP37157-pretreated cells. f, Mitochondrial Ca2+ transient frequency (times per hour) in the cells at interphase or in mitosis. n = 171 interphase cells and 84 mitotic cells from 3 independent experiments. g, Quantification of the distribution of mitochondrial Ca2+ transients in prometaphase or metaphase. n = 3 independent experiments. (h-k) Representative mitotic mitochondrial Ca2+ transient in rat kangaroo kidney epithelial Ptk1 cells (h), NIH3T3 mouse embryonic fibroblast cells (i), hepatoma carcinoma cell HepG2 (j) and LM3 (k). All scale bars indicate 10 μm. Data in a-e,h-k represent three independent experiments with similar results. Data are shown as mean ± s.e.m. Unpaired two-sided student’s t-test was performed in e,g; unpaired two sided Mann Whitney test was performed in f. Source data are provided in Supplementary Table 4.
a, Representative images of mitochondrial Ca2+ dynamics (4mt-GCaMP6) in control or MCU knockdown HeLa/RFP-H2B cells during mitosis, as described in Fig. 1c-e. b, Resting mitochondrial Ca2+ levels (4mt-GCaMP6) during mitosis were measured in control and MCU knockdown HeLa/RFP-H2B cells. n = 51 control cells and 40 MCU silenced cells. The experiment was repeated twice independently. c, The lengths of time from NEB to anaphase onset in control cells, MCU siRNA #1 cells and #2 cells were analyzed, as described in Fig. 2c. n = 147, 105, 80 cells (from left to right). Data are from two independent experiments. MCU protein expression was verified by Western Blot. d, The lengths of time from NEB to anaphase onset in RPE, MB-231, U251 and U2OS cells transfected with indicated siRNAs. n = 36, 15, 56, 49, 57, 56, 50, 50 cells (from left to right). The experiment was repeated twice. MCU protein expression was verified by Western Blot. e, EdU staining (green) of HeLa cells transfected with indicated siRNAs. The experiment was repeated three times independently. f, Percentage of EdU-positive HeLa cells based on images in e. n = 3 independent experiments. g, Relative mean traces of mitochondrial Ca2+ level (indicated by luminescence of mtAequorin) in HeLa cells expressing vector, siRNA-resistant MCUWT or MCUMut (MCUD261E, D264E) transfected with indicated siRNAs. 100 μM histamine was added as the arrow indicated. The peak value of the control cells was set to 1. h, Quantification of the maximal amplitudes of the traces in g. n = 3 replicate samples. Data are representative of three independent experiments. i, MCU protein expression was verified by Western Blot. The experiment was repeated three times independently with similar results. All scale bars indicate 10 μm. All data are shown as mean ± s.e.m. One-way ANOVA was performed in c,h; Unpaired two-sided student’s t-test was performed in f; Unpaired two sided Mann Whitney test was performed in b,d. Scanned images of unprocessed blots are shown in Supplementary Fig. 8. Source data are provided in Supplementary Table 4.
a, Embryos were obtained by heterozygous crosses. Wild type (+/+) and MCU knockout embryos (-/-) harvested at E13.5. At this time point, some MCU-/- embryos have already died (#4) while other show a mild size reduction (#5) or appear normal (#6). b, Embryos were obtained by heterozygous crosses and isolated at the indicated time of gestation. Genotypes of embryos were determined by PCR. Number of each genotype was recorded and the analyzed percentage was indicated in bracket. c, Selected frames from time-lapse movies of mitotic progression and subsequent cell death of representative primary wild-type and MCU knockout fetal liver cells stained with SiR-Hoechst. The time on the images is in minute. Scale bar, 10 μm. Cell death percentage in mitosis were analyzed (right panel). Data are shown as mean ± s.e.m. n = 3 pairs of mice. Unpaired two-sided student’s t-test was performed. d, TUNEL staining of E12.5 whole embryos with high power view of corresponding fetal liver shown directly below (left panel). The quantification of percent TUNEL positive cells was shown (right panel). Scale bar, 100 μm. Data are shown as mean ± s.e.m. n = 3 pairs of mice. Unpaired two-sided student’s t-test was performed. e, Available CD1 mice were obtained by heterozygous crosses. Genotypes were determined by PCR. Number of each genotype was recorded and analyzed percentage was shown. Source data are provided in Supplementary Table 4.
Supplementary Figure 4 Mitochondrial Ca2+ transients boost mitochondrial ATP production and don’t alter cytosolic Ca2+ signaling.
a, Snapshot of cytosolic Ca2+ (upper, green) and mitochondrial Ca2+ (lower, red) transient images from time-lapse movies of representative HeLa cells co-expressing GCaMP6 and 4mt-RCaMPh during mitosis. The time on the images is in minute. Scale bar, 10 μm. (b and c) Amplitude (b) and frequency (c) quantification of cytosolic Ca2+ transients in control and MCU knockdown mitotic cells. n = 55 control cells and 62 MCU silenced cells from three independent experiments. d, Resting cytosolic Ca2+ levels (GCaMP6) during mitosis were measured in control and MCU knockdown HeLa cells. n = 62 control cells and 74 MCU silenced cells. The experiment was repeated three times independently. e, Representative traces of mitochondrial Ca2+ (4mt-RCaMPh) and mitochondrial ATP (4mt-ATeam1.03) dynamics in the presence of 10 μM oligomycin or not. 100 μM histamine was added as the arrow indicated. The experiment was repeated three times independently. All data are shown as mean ± s.e.m. Unpaired two-sided student’s t-test was performed in b,d; Unpaired two-sided Mann Whitney test was performed in c. Source data are provided in Supplementary Table 4.
Supplementary Figure 5 MCU-mediated ATP production is required for proper microtubule dynamics during mitosis.
(a and b) Images from time-lapse movies of a representative HeLa cell expressing ATeam1.03 (pseudocolored) after PBS or 5 mM ATP addition. Cytosolic ATP level change was measured by the emission ratio (YFP/CFP) of ATeam1.03 and shown in b. n = 12 cells for PBS and 14 cells for ATP treatment. The time on the images is in minute. Scale bar, 10 μm. The experiment was repeated three times independently. c, HeLa cells were treated with the indicated siRNAs before taxol arrest. For the last 2 h before shake-off, MG132 was added. Then taxol-arrested cells were shaken off and treated with ZM447439 for the indicated times. Cdc20 was immunoprecipitated, and co-precipitated Mad2 was analyzed by immunoblotting. The experiment was repeated twice independently. d, Quantification of spindle tubulin levels in Fig. 3f. n = 45, 44, 43, 53, 45, 45 cells (from left to right). The experiment was repeated twice independently. e, HeLa cells were pretreated with 5 mM ATP or AMP for 4 hrs followed by washout. Cytosolic Ca2+ levels were measured by fluorescence of GCaMP6 following 10 μM histamine stimulation. f, Quantification of the maximal amplitudes of the traces in e. n = 30 cells for each group. Data are representative of three independent experiments with similar results. All data are shown as mean ± s.e.m. All P values were calculated using one-way ANOVA. Source data are provided in Supplementary Table 4.
a, 293T cells were transfected with vectors expressing Flag-tagged MCU or Flag-tagged MCUS57A. Cell lysates were analyzed by Western Blot. The experiment was repeated three times independently. b, HeLa cells were transfected with siRNAs as indicated. After 72h, cell lysates were analyzed by Western Blot. The experiment was repeated three times independently. c, WT (parental) or AMPK DKO HeLa cells were treated with DMSO, 300 μM A-769662, 2 mM metformin for 2–4 hrs or 5μM Ionomycin for 1 h followed by Western blotting analysis with indicated antibodies. The experiment was repeated three times independently. d, In vitro kinase assay using active, recombinant AMPK (α1, β1, γ1) holoenzyme with GST-MCUWT or GST-MCU NTD (1–165aa) as substrates in the presence of ATP for 45 min followed by Western blotting analysis with indicated antibodies. The experiment was repeated three times independently. e, HeLa cell mitochondria were isolated and proteins were extracted with 0.1 M Na2CO3 at pH 11.5. Both the soluble fractions (S) and the insoluble pellet (P) were analyzed by Western Blot. The experiment was repeated twice independently. f, Isolated mitochondria from mitotic HeLa cells were treated with Proteinase K or not and stained with indicated antibodies. Scale Bar, 1 μm. The experiment was repeated twice independently. g, Asynchronous (Asy) and nocodazole-arrested (M) extracts from WT (parental) or AMPK DKO U2OS and HEK293 cells were immunoblotted with indicated antibodies. The experiment was repeated twice independently. h, Representative immunofluorescent images of control and MCU siRNA transfected cells stained for pMCU-Ser57 (green), mitochondria (HSP60, red) and DNA (Hoechst, blue), respectively. Scale Bar, 10 μm. The experiment was repeated three times independently. Scanned images of unprocessed blots are shown in Supplementary Fig. 8.
a, Representative immunofluorescent images of MCUWT-GFP, MCUS57A-GFP and MCUS57D-GFP transfected HeLa cells stained for mitochondria inner membrane (COXIV, red) and DNA (Hoechst, blue), respectively. Scale Bar, 10 μm. b, HEK293T cells were transfected with MCUWT-Flag, MCUS57A-Flag and MCUS57D-Flag. Cell lysates were fractionated by gel filtration chromatography and immunoblotted. The experiment was repeated twice independently. c, Representative traces of mitochondrial Ca2+ dynamics following 10 μM histamine treatment indicated by fluorescence of 4mt-GCaMP6 in WT (parental), AMPK DKO HeLa cells or HeLa cells pretreated with 300μM A769662 for 4 hrs followed by washout. Data are shown as mean ± s.e.m. n = 30 cells for each group. d, Quantification of the maximal amplitudes of the mitochondrial Ca2+ traces in c. n = 30 cells for each group. One-way ANOVA was performed. e, Phosphorylation of MCU and AMPK in c was analyzed by Western Blot. f, Representative traces of mitochondrial Ca2+ dynamics following 10 μM histamine treatment indicated by fluorescence of 4mt-GCaMP6 in MCU depleted cells stably transfected with MCUWT, MCUS57A or MCUS57D pretreated with or not 300μM A769662 for 4 hrs followed by washout. g. Quantification of the maximal amplitudes of the mitochondrial Ca2+ traces in f. n = 30 cells for each group. Data are shown as mean ± s.e.m. One-way ANOVA was performed. Data in a,c-g represent three independent experiments with similar results. Scanned images of unprocessed blots are shown in Supplementary Fig. 8. Source data are provided in Supplementary Table 4.
Pictures of individual blots shown throughout this study.
Supplementary Figures 1–8 and legends for Supplementary Tables 1–4 and Supplementary Videos 1–7.
List of oligonucleotides used in this study.
List of antibodies used in this study.
List of reagents used in this study.
Statistics source data.
A representative mitotic mitochondrial Ca2+ transient in HeLa cell #1.
A representative mitotic mitochondrial Ca2+ transient in HeLa cell #2.
A representative M phase progression in HeLa GFP–H2B cell transfected with control siRNA.
A representative M phase progression in HeLa GFP–H2B cell transfected with MCU #1 siRNA.
A representative M phase progression in HeLa GFP–H2B cell transfected with MCU #2 siRNA.
RFP–Mad2 disappearance in a representative HeLa GFP–H2B cell transfected with control siRNA.
RFP–Mad2 disappearance in a representative HeLa GFP–H2B cell transfected with MCU siRNA.
About this article
Cite this article
Zhao, H., Li, T., Wang, K. et al. AMPK-mediated activation of MCU stimulates mitochondrial Ca2+ entry to promote mitotic progression. Nat Cell Biol 21, 476–486 (2019). https://doi.org/10.1038/s41556-019-0296-3
Adipose-derived stem cells alleviate liver injury induced by type 1 diabetes mellitus by inhibiting mitochondrial stress and attenuating inflammation
Stem Cell Research & Therapy (2022)
Nature Methods (2022)
Mitochondrial homeostasis regulates definitive endoderm differentiation of human pluripotent stem cells
Cell Death Discovery (2022)
AMPK-deficiency forces metformin-challenged cancer cells to switch from carbohydrate metabolism to ketogenesis to support energy metabolism
CLIC1 Inhibition Protects Against Cellular Senescence and Endothelial Dysfunction Via the Nrf2/HO-1 Pathway
Cell Biochemistry and Biophysics (2021)