A new study reports that common mitochondrial DNA variants in specific haplogroups induce metabolic alterations that affect the onset of common age-related diseases. Unravelling the role of this subtle, long-lasting burden of mitochondrial DNA variants on kidney homeostasis could provide novel insights into the pathophysiology of chronic kidney disease.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Hasegawa, S. & Inagi, R. Organelle stress and crosstalk in kidney disease. Kidney360 1, 1157–1164 (2020).
Cai, N. et al. Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases. Nat. Med. 27, 1564–1575 (2021).
Marom, S., Friger, M. & Mishmar, D. MtDNA meta-analysis reveals both phenotype specificity and allele heterogeneity: a model for differential association. Sci. Rep. 7, 43449 (2017).
Bhargava, P. & Schnellmann, R. G. Mitochondrial energetics in the kidney. Nat. Rev. Nephrol. 13, 629–646 (2017).
Chung, K. W. et al. Mitochondrial damage and activation of the STING pathway lead to renal inflammation and fibrosis. Cell Metab. 30, 784–799 (2019).
Maekawa, H. et al. Mitochondrial damage causes inflammation via cGAS-STING signaling in acute kidney injury. Cell Rep. 29, 1261–1273 (2019).
Tran, M. T. et al. PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection. Nature 531, 528–532 (2016).
Hasegawa, S. & Inagi, R. Harnessing metabolomics to describe the pathophysiology underlying progression in diabetic kidney disease. Curr. Diab. Rep. 21, 21 (2021).
Galvan, D. L. et al. Drp1S600 phosphorylation regulates mitochondrial fission and progression of nephropathy in diabetic mice. J. Clin. Invest. 129, 2807–2823 (2019).
Hasegawa, S. et al. The oral hypoxia-inducible factor prolyl hydroxylase inhibitor enarodustat counteracts alterations in renal energy metabolism in the early stages of diabetic kidney disease. Kidney Int. 97, 934–950 (2020).
Acknowledgements
The authors’ work is supported by a Grant-in-Aid for Early-Career Scientists (JSPS KAKENHI grant 21K16159 to SH), a Grant-in-Aid for Scientific Research (B) (JSPS KAKENHI grant 21H02824 to R.I.), and grants from MSD Life Science Foundation (to S.H.), the Cell Science Research Foundation (to S.H.), Takeda Science Foundation (to S.H.), and Kyowa Kirin (to R.I.).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The Division of CKD pathophysiology, University of Tokyo, Japan, is financially supported by grants from Kyowa Kirin that are not directly related to this work.
Rights and permissions
About this article
Cite this article
Hasegawa, S., Inagi, R. The subtle long-lasting burden of mitochondrial DNA variants. Nat Rev Nephrol 18, 4–5 (2022). https://doi.org/10.1038/s41581-021-00500-9
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41581-021-00500-9
