Article
|
Open Access
Featured
-
-
Article
| Open Access
PsAF5 functions as an essential adapter for PsPHB2-mediated mitophagy under ROS stress in Phytophthora sojae
ROS is an important defense means against pathogens for host. Here the authors show that PsAF5 functions as a mitophagy adapter and regulates mitochondrial homeostasis in Phytophthora sojae under ROS stress, which is crucial for its infection.
- Wenhao Li
- , Hongwei Zhu
- & Xili Liu
-
Article
| Open Access
ALLO-1- and IKKE-1-dependent positive feedback mechanism promotes the initiation of paternal mitochondrial autophagy
Allophagy eliminates paternal mitochondria in C. elegans embryos. This study reveals that an autophagy adaptor, ALLO-1, recognizes cargos and initiates autophagosome formation by gathering with the ULK complex in an IKKE-1 kinase-dependent manner.
- Taeko Sasaki
- , Yasuharu Kushida
- & Miyuki Sato
-
Article
| Open Access
Nutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control
The quality of germline mitochondria is essential for producing healthy oocytes. Here, Ng, Chan and Pek report a stable intron that modulates germline mitochondrial quality control during fasting, heat stress and aging.
- Annabel Qi En Ng
- , Seow Neng Chan
- & Jun Wei Pek
-
Article
| Open Access
Relaxation of mitochondrial hyperfusion in the diabetic retina via N6-furfuryladenosine confers neuroprotection regardless of glycaemic status
Restoring mitochondrial function has emerged as a promising therapeutic strategy for diabetic retinopathy. Here, the authors show that mitochondrial hyperfusion blunts mitophagy during the disease process, and that rescuing this process pharmacologically confers retinal neuroprotection independent of an improved glycaemic status in type-1 diabetic mice.
- Aidan Anderson
- , Nada Alfahad
- & Jose R. Hombrebueno
-
Article
| Open Access
Upregulated pexophagy limits the capacity of selective autophagy
An accumulation of one substrate of selective autophagy can lead to autophagic degradation deficiencies. Here, the authors show that a pathogenic increase in a single autophagy pathway restricts another by consuming the cell’s autophagy capacity.
- Kyla Germain
- , Raphaella W. L. So
- & Peter K. Kim
-
Article
| Open Access
GRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis
Cytoskeletal remodeling is known to facilitate mitophagy, but the mechanism is not fully understood. Here, the authors show that damaged mitochondria recruit a RhoA GTPase activating protein that promotes their capture and encasement by autophagosomes.
- Qiang Zhu
- , Matthew E. Combs
- & Joan M. Taylor
-
Article
| Open Access
PPTC7 maintains mitochondrial protein content by suppressing receptor-mediated mitophagy
The mitochondrial phosphatase PPTC7 has previously been linked to the maintenance of mitochondrial content, but the mechanisms underlying this phenotype remain unclear. Here, the authors demonstrate that loss of Pptc7 results in metabolic defects and further suggest that PPTC7 is a regulator of receptor-mediated mitophagy.
- Natalie M. Niemi
- , Lia R. Serrano
- & David J. Pagliarini
-
Article
| Open Access
PINK1 and Parkin regulate IP3R-mediated ER calcium release
Loss of two PD genes, PINK1 and Parkin, leads to a robust increase in ER calcium release. Here, the authors show that suppression of IP3R activity via inhibiting CISD1 is sufficient to rescue the PD-related phenotypes in PINK1 or Parkin null animal models.
- Su Jin Ham
- , Heesuk Yoo
- & Jongkyeong Chung
-
Article
| Open Access
Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism
Phospholipase D3 polymorphisms are linked to late-onset Alzheimer’s disease but the mechanisms are not understood. Van Acker and colleagues show that Phospholipase D3 processes mitochondrial DNA in lysosomes to maintain lysosomal homeostasis and proper degradation of the amyloid precursor protein.
- Zoë P. Van Acker
- , Anika Perdok
- & Wim Annaert
-
Article
| Open Access
Genetically prolonged beige fat in male mice confers long-lasting metabolic health
Beige adipocytes quickly transition into white adipocytes upon the removal of stimuli, limiting their therapeutic potential for chronic metabolic diseases. In this study, the authors show that inhibiting Cdkn2a-Becn1 mediated autophagy can maintain beige adipocytes and provide long term metabolic health benefits in mice.
- Ruifan Wu
- , Jooman Park
- & Yuwei Jiang
-
Article
| Open Access
Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA
Mitochondrial quality control mechanisms prevent damage accumulation, including in mitochondrial DNA (mtDNA). Here, Sen et al. show that altered mtDNA elicits local rearrangements in mitochondrial membrane potential and cristae structure, with mtDNA eliminated through VPS35 endosomes.
- Ayesha Sen
- , Sebastian Kallabis
- & David Pla-Martín
-
Article
| Open Access
TraB family proteins are components of ER-mitochondrial contact sites and regulate ER-mitochondrial interactions and mitophagy
Contact sites permit the exchange of signals and materials between organelles. Here the authors characterize a protein complex associated with an ER-mitochondrial contact site in Arabidopsis that is required for mitochondrial function and mitochondrial turnover
- Chengyang Li
- , Patrick Duckney
- & Pengwei Wang
-
Article
| Open Access
Protein import motor complex reacts to mitochondrial misfolding by reducing protein import and activating mitophagy
Mitophagy activation is mediated by mitochondrial depolarization. Here, the authors show that mitochondrial protein misfolding can activate mitophagy in a depolarization-independent manner mediated by a protein import reduction.
- Jonas Benjamin Michaelis
- , Melinda Elaine Brunstein
- & Christian Münch
-
Article
| Open Access
A degradative to secretory autophagy switch mediates mitochondria clearance in the absence of the mATG8-conjugation machinery
The mechanisms underlying mitochondrial quality control are not fully understood. Here the authors identify a switch from degradative to secretory autophagy in the absence of the mATG8-conjugation system, termed Autophagic Secretion of Mitochondria.
- Hayden Weng Siong Tan
- , Guang Lu
- & Han-Ming Shen
-
Article
| Open Access
Pantothenate kinase 2 interacts with PINK1 to regulate mitochondrial quality control via acetyl-CoA metabolism
PKAN and PD are two distinct diseases with overlapping pathophysiology. Here, authors show that their pathogenic genes PANK2 and PINK1 interact. PANK2 regulates mitophagy via CoA metabolism, while PINK1 supervises PANK2 translation on mitochondria.
- Yunpeng Huang
- , Zhihui Wan
- & Bing Zhou
-
Article
| Open Access
Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming
Lactic acidosis is a metabolic state that occurs in injured tissues. Here the authors show that macrophages, in order to remain functional in acidosis, reduce their mitochondrial mass by mitophagy and rely on autophagy for survival, with mitochondrial integrity retained using acetoacetate as alternative fuel.
- Clément Adam
- , Léa Paolini
- & Pascale Jeannin
-
Article
| Open Access
GAK and PRKCD are positive regulators of PRKN-independent mitophagy
The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remain elusive. Here the authors use an siRNA library to screen lipid-binding proteins, and identify the kinases GAK and PRKCD as positive regulators of PRKN-independent mitophagy.
- Michael J. Munson
- , Benan J. Mathai
- & Anne Simonsen
-
Article
| Open Access
Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates
How phase separation participates in mitophagy remains unclear. Here the authors show that Nur77 and p62/SQSTM1 through “head-to-head” and “tail-to-tail” interactions form membraneless condensates capable of sequestering dysfunctional mitochondria and tethering them to autolysosome for degradation.
- Shuang-zhou Peng
- , Xiao-hui Chen
- & Xiao-kun Zhang
-
Article
| Open Access
BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects
Stress-induced glucocorticoids cause mitochondrial damage in neurons, but they are not cleared by mitophagy. Here, the authors show that glucocorticoids inhibit NIX-dependent basal mitophagy, contributing to neurodegeneration in a mouse model that can be reversed by pretreatment with a NIX enhancer.
- Gee Euhn Choi
- , Hyun Jik Lee
- & Ho Jae Han
-
Article
| Open Access
Pharmacological targeting of MCL-1 promotes mitophagy and improves disease pathologies in an Alzheimer’s disease mouse model
Previous work suggests that mitophagy in neurons is could be therapeutic in Alzheimer’s disease (AD). Here, the authors screen a library of drugs and identify UMI-77, a mitophagy inducer with beneficial effects in an AD mouse model, by binding MCL-1, which they identify as a mitophagy receptor.
- Xufeng Cen
- , Yanying Chen
- & Hongguang Xia
-
Article
| Open Access
NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome
The molecular mechanisms of mitochondrial dysfunction in the premature ageing Werner syndrome were elusive. Here the authors show that NAD+ depletion-induced impaired mitophagy contributes to this phenomenon, shedding light on potential therapeutics.
- Evandro F. Fang
- , Yujun Hou
- & Vilhelm A. Bohr
-
Article
| Open Access
DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
Muscle loss is associated with altered expression of proteins involved in mitochondrial homeostasis, but whether this is causative remains unclear. Here, the authors show that genetic ablation of the pro-fission protein DRP1 leads to accumulation of abnormal mitochondria that induce muscle atrophy by altering Ca2+ homeostasis and cellular stress responses.
- Giulia Favaro
- , Vanina Romanello
- & Marco Sandri
-
Article
| Open Access
STX17 dynamically regulated by Fis1 induces mitophagy via hierarchical macroautophagic mechanism
Mitophagy plays a critical role in cellular homeostasis, and PINK1/Parkin-mediated mitophagy is the most thoroughly characterized. Here, Xian et al. show that STX17 induces mitophagy via a macroautophagy pathway regulated by Fis1, by a PINK1/Parkin-independent route.
- Hongxu Xian
- , Qiaoyun Yang
- & Yih-Cherng Liou
-
Article
| Open Access
Reversible induction of mitophagy by an optogenetic bimodular system
Autophagic degradation of mitochondria (mitophagy) is a key quality control mechanism in cellular homeostasis, and its misregulation is involved in neurodegenerative diseases. Here the authors develop an optogenetic system for reversible induction of mitophagy and validate its use in cell culture and zebrafish embryos.
- Pasquale D’Acunzo
- , Flavie Strappazzon
- & Francesco Cecconi
-
Article
| Open Access
Omegasome-proximal PtdIns(4,5)P2 couples F-actin mediated mitoaggregate disassembly with autophagosome formation during mitophagy
Autophagic cells coordinate substrate remodeling with sequestration during autophagosome formation. Here, the authors show that during Parkin-mediated mitophagy, mitochondria are disassembled into progressively smaller aggregates near autophagy initiation sites in a PtdIns(4,5)P2-dependent manner.
- Cheng-Wei Hsieh
- & Wei Yuan Yang
-
Article
| Open Access
LC3/GABARAPs drive ubiquitin-independent recruitment of Optineurin and NDP52 to amplify mitophagy
Selective autophagy receptors are thought to selectively recruit Atg8 positive membranes to cargo via their LIR motif. Here, the authors show the LIR motifs in OPTN and NDP52 are dispensable for selectivity, functioning instead to recruit additional receptors and amplify mitophagy.
- Benjamin Scott Padman
- , Thanh Ngoc Nguyen
- & Michael Lazarou
-
Article
| Open Access
HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα
Mitophagy is crucial for mitochondrial quality control and maintenance of cellular homeostasis. Here the authors identify an E3 ubiquitin ligase, HUWE1, that collaborates with LC3-interacting protein AMBRA1 to induce mitochondrial clearance.
- Anthea Di Rita
- , Angelo Peschiaroli
- & Francesco Cecconi
-
Article
| Open Access
Autophagy promotes the survival of dormant breast cancer cells and metastatic tumour recurrence
Highly metastatic dormant cancer cells contribute to breast cancer recurrence, but the underlying mechanism is less understood. Here, the authors show that dormant breast cancer cells depend on autophagy to ensure their long term survival and distant recurrence
- Laura Vera-Ramirez
- , Suman K. Vodnala
- & Jeffrey E. Green
-
Article
| Open Access
Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy
Exercise is associated with biogenesis and removal of dysfunctional mitochondria. Here the authors use a mitochondrial reporter gene to demonstrate the occurrence of mitophagy following exercise in mice, and show this is dependent on AMPK and ULK1 signaling.
- Rhianna C. Laker
- , Joshua C. Drake
- & Zhen Yan
-
Article
| Open Access
Multiple truncated isoforms of MAVS prevent its spontaneous aggregation in antiviral innate immune signalling
MAVS is an essential component of the pathogen-sensing machinery, and functions by forming prion-like filaments. Here the authors show that alternatively translated forms of truncated endogenous MAVS can prevent spontaneous aggregation and degradation in cells to sustain MAVS-mediated immune signalling.
- Nan Qi
- , Yuheng Shi
- & Fajian Hou
-
Article
| Open Access
Structure-guided mutagenesis reveals a hierarchical mechanism of Parkin activation
Parkin and PINK1 are involved in damaged mitochondria clearance; however the sequence of events of Parkin activation is not clear. Here, the authors show that binding to phospho-ubiquitin on mitochondria enables Parkin phosphorylation, which allows Repressor Element of Parkin removal, E3 ligase activation and mitophagy.
- Matthew Y. Tang
- , Marta Vranas
- & Edward A. Fon
-
Article
| Open Access
A Rab5 endosomal pathway mediates Parkin-dependent mitochondrial clearance
Damaged mitochondria are normally cleared through canonical and alternative autophagy pathways. Here, the authors report that mitochondria can be cleared through an autophagy-independent endosomal-lysosomal pathway that depends on Parkin-dependent sequestration of mitochondria in Rab5-positive early endosomes.
- Babette C. Hammerling
- , Rita H. Najor
- & Åsa B. Gustafsson
-
Article
| Open Access
Selective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila
Heteroplasmy, in which mutant and wild-type mitochondrial DNA (mtDNA) coexist in a cell, can result in diseases. Here the authors generate transgenic flies with heteroplasmic mtDNA in flight muscles, and show that stimulation of autophagy, or a decrease in mitofusin, promotes clearance of mutant mtDNA.
- Nikolay P. Kandul
- , Ting Zhang
- & Ming Guo
-
Article
| Open Access
Structural insights into the interaction and disease mechanism of neurodegenerative disease-associated optineurin and TBK1 proteins
Mutations in optineurin that cause defects in the interaction with TBK1 are associated with neurodegenerative diseases. Here, the authors report the structure of this complex, and outline a general binding mode for these proteins.
- Faxiang Li
- , Xingqiao Xie
- & Lifeng Pan
-
Article
| Open Access
Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
The physiological role of crosstalk between mesenchymal stem cells (MSC) and macrophages is unclear. Here, Phinney et al. show that MSCs transfer mitochondria to macrophages under oxidative stress, and desensitize macrophages to mitochondria by using microvesicles to repress Toll receptor signalling.
- Donald G. Phinney
- , Michelangelo Di Giuseppe
- & Luis A. Ortiz
-
Article
| Open Access
Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation
Atg32 is required for mitophagy in yeast, however, a mammalian homologue of this protein has not been identified. Murakawaet al. identify Bcl-2-like protein 13 as a functional homologue of Atg32 in mammalian cells, and show that this protein can rescue mitophagy in Atg32-deficient yeast cells.
- Tomokazu Murakawa
- , Osamu Yamaguchi
- & Kinya Otsu
-
Article |
Genetic deficiency of the mitochondrial protein PGAM5 causes a Parkinson’s-like movement disorder
Mitophagy selectively disposes of dysfunctional mitochondria and defects in this process lead to a variety of mitochondrial diseases. Here the authors report that the mitochondrial protein PGAM5 is required for the stabilization of mitophagy-inducing protein PINK1, and that mice deficient for the gene coding for PGAM5 show signs of neurodegeneration.
- Wei Lu
- , Senthilkumar S. Karuppagounder
- & Michael Lenardo
-
Article |
Involvement of mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy
The extent to which damaged and undamaged structures can be segregated within the mitochondrial network during mitophagy is unclear. Abeliovich et al. show that mitochondrial matrix proteins undergo mitophagic degradation at different rates, and that this depends on regulators of mitochondrial dynamics.
- Hagai Abeliovich
- , Mostafa Zarei
- & Joern Dengjel
-
Article |
Bit-by-bit autophagic removal of parkin-labelled mitochondria
Dysfunctional mitochondria are degraded by mitophagy, but how large mitochondria are packed into small autophagic vesicles is unclear. Here the authors show that dysfunctional mitochondria are degraded in a bit-by-bit fashion initiated at sites where parkin-labelled mitochondrial tubules and the endoplasmic reticulum intersect.
- Jin-Yi Yang
- & Wei Yuan Yang
-
Article |
Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart
Damaged mitochondria are removed from cells through a process called mitophagy. Here, Hoshino et al. show that the cytosolic fraction of the protein p53 inhibits mitophagy by sequestering the mitophagy regulator Parkin, leading to impaired mitochondrial integrity and cardiac function in aged or damaged mouse hearts.
- Atsushi Hoshino
- , Yuichiro Mita
- & Satoaki Matoba
-
Article |
Selective escape of proteins from the mitochondria during mitophagy
Damaged mitochondria are eliminated from the cell by a form of autophagy called mitophagy. Here the authors show that during mitophagy, specific proteins are rescued from degradation by evacuation from the mitochondria to the endoplasmic reticulum.
- Shotaro Saita
- , Michiko Shirane
- & Keiichi I. Nakayama
NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia