bims-mikwok 2022-11-13 papers

bims-mikwok

Biomed News

on Mitochondrial quality control

Issue of 2022‒11‒13
twelve papers selected by
Avinash N. Mukkala, University of Toronto

AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology.
Novel protein complexes containing autophagy and UPS components regulate proteasome-dependent PARK2 recruitment onto mitochondria and PARK2-PARK6 activity during mitophagy.
DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion.
Augmenter of liver regeneration reduces mitochondria-derived ROS and NLRP3 inflammasome activation through PINK1/Parkin-mediated mitophagy in ischemia-reperfusion-induced renal tubular injury.
Tissue imaging reveals disruption of epithelial mitochondrial networks and loss of mitochondria-associated cytochrome-C in inflamed human and murine colon.
Ubiquitin-mediated mitochondrial regulation by MITOL/MARCHF5 at a glance.
Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA.
SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia.
Mitochondrial Transplantation Moderately Ameliorates Retinal Degeneration in Royal College of Surgeons Rats.
Mitochondrial dynamics, Leydig cell function, and age-related testosterone deficiency.
Endosymbiotic selective pressure at the origin of eukaryotic cell biology.
Connexin 43 hemichannels regulate mitochondrial ATP generation, mobilization, and mitochondrial homeostasis against oxidative stress.

Sci Adv. 2022 Nov 11. 8(45): eabo7956

AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology.

Lisa Tilokani, Fiona M Russell, Stevie Hamilton, Daniel M Virga, Mayuko Segawa, Vincent Paupe, Anja V Gruszczyk, Margherita Protasoni, Luis-Carlos Tabara, Mark Johnson, Hanish Anand, Michael P Murphy, D Grahame Hardie, Franck Polleux, Julien Prudent.

Mitochondria are dynamic organelles that undergo membrane remodeling events in response to metabolic alterations to generate an adequate mitochondrial network. Here, we investigated the function of mitochondrial fission regulator 1-like protein (MTFR1L), an uncharacterized protein that has been identified in phosphoproteomic screens as a potential AMP-activated protein kinase (AMPK) substrate. We showed that MTFR1L is an outer mitochondrial membrane-localized protein modulating mitochondrial morphology. Loss of MTFR1L led to mitochondrial elongation associated with increased mitochondrial fusion events and levels of the mitochondrial fusion protein, optic atrophy 1. Mechanistically, we show that MTFR1L is phosphorylated by AMPK, which thereby controls the function of MTFR1L in regulating mitochondrial morphology both in mammalian cell lines and in murine cortical neurons in vivo. Furthermore, we demonstrate that MTFR1L is required for stress-induced AMPK-dependent mitochondrial fragmentation. Together, these findings identify MTFR1L as a critical mitochondrial protein transducing AMPK-dependent metabolic changes through regulation of mitochondrial dynamics.

DOI: https://doi.org/10.1126/sciadv.abo7956
Cell Death Dis. 2022 Nov 10. 13(11): 947

Novel protein complexes containing autophagy and UPS components regulate proteasome-dependent PARK2 recruitment onto mitochondria and PARK2-PARK6 activity during mitophagy.

Nur Mehpare Kocaturk, Nesibe Peker, Karin Eberhart, Yunus Akkoc, Gamze Deveci, Joern Dengjel, Devrim Gozuacik.

Autophagy is an evolutionarily conserved eukaryotic cellular mechanism through which cytosolic fragments, misfolded/aggregated proteins and organelles are degraded and recycled. Priming of mitochondria through ubiquitylation is required for the clearance the organelle by autophagy (mitophagy). Familial Parkinson's Disease-related proteins, including the E3-ligase PARK2 (PARKIN) and the serine/threonine kinase PARK6 (PINK1) control these ubiquitylation reactions and contribute to the regulation of mitophagy. Here we describe, novel protein complexes containing autophagy protein ATG5 and ubiquitin-proteasome system (UPS) components. We discovered that ATG5 interacts with PSMA7 and PARK2 upon mitochondrial stress. Results suggest that all three proteins translocate mitochondria and involve in protein complexes containing autophagy, UPS and mitophagy proteins. Interestingly, PARK2 and ATG5 recruitment onto mitochondria requires proteasome components PSMA7 and PSMB5. Strikingly, we discovered that subunit of 20 S proteasome, PSMA7, is required for the progression of PARK2-PARK6-mediated mitophagy and the proteasome activity following mitochondrial stress. Our results demonstrate direct, dynamic and functional interactions between autophagy and UPS components that contribute to the regulation of mitophagy.

DOI: https://doi.org/10.1038/s41419-022-05339-x
Free Radic Biol Med. 2022 Oct 28. pii: S0891-5849(22)00946-7. [Epub ahead of print]193(Pt 1): 430-436

DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion.

Alex Gallinat, Aleksandar Rakovic, Christine Klein, Lina Badimon.

  The early-onset Parkinson's disease protein DJ-1 is a multifunctional protein that plays a protective role against ischemia and reperfusion (I/R) injury and oxidative stress. Despite lacking a canonical RNA-binding domain DJ-1 exhibits RNA-binding activity and multiple transcripts have been identified. However, no functional characterization has been provided to date. Here, we have investigated the DJ-1-interacting transcripts, as well as the role of DJ-1 RNA-binding activity during ischemia and reperfusion. Among the identified DJ-1-interacting transcripts, we have distinguished a significant enrichment of mRNAs encoding mitochondrial proteins. The effects of DJ-1 depletion on mitochondrial protein expression and mitochondrial morphology were investigated using a CRISPR/Cas9 generated DJ-1 knockout (DJ-1KO) cell model. DJ-1 depletion resulted in increased MTND2 protein expression in resting cells; however, after exposure to I/R, MTND2 levels were significantly reduced with respect to wild type cells. Increased mitochondrial fission was consistently found in DJ-1KO cells after I/R exposure. MTND2 transcript binding to DJ-1 was increased during ischemia. Our results indicate that the RNA-binding activity of DJ-1 shield mitochondrial transcripts from oxidative damage.

Keywords:  DJ-1; Ischemia; Ischemia/reperfusion; Mitochondria; PARK7; RNA-Binding

DOI:  https://doi.org/10.1016/j.freeradbiomed.2022.10.315
Apoptosis. 2022 Nov 12.

Augmenter of liver regeneration reduces mitochondria-derived ROS and NLRP3 inflammasome activation through PINK1/Parkin-mediated mitophagy in ischemia-reperfusion-induced renal tubular injury.

Dongju Zhu, Jie Zhong, Xuefeng Gong, Xiang Wu.

  Ischemia-reperfusion (IR) injury is one of the main causes of acute kidney disease (AKI). Several studies have shown that mitochondrial damage, which leads to increased production of reactive oxygen species (ROS), plays a vital role in the pathogenesis of IR-induced AKI. Increased ROS production can cause oxidative damage and activate the inflammasome in renal tubular cells, ultimately resulting in apoptosis or necrosis. Mitophagy is a type of selective autophagy that plays a protective role in AKI by regulating the quality of mitochondria and reducing the production of ROS. We previously reported that the augmenter of liver regeneration (ALR) exhibits antiapoptotic and antioxidant functions, although the precise mechanisms of action need to be studied further. In the current study, ALR was overexpressed and an in vitro model of IR injury was constructed. The overexpression of ALR reduced the production of mitochondria-derived ROS (mtROS), the activation of the NLRP3 inflammasome, and the rate of apoptosis. Moreover, this suppression of mtROS production and inflammasome activation was mediated through the PTEN-induced kinase 1 (PINK1)/Parkin pathway of mitophagy. These results suggest that ALR can alleviate IR-induced apoptosis via the PINK1/Parkin mitophagy pathway to reduce the production of mtROS and limit the activation of the NLRP3 inflammasome.

Keywords:  Acute kidney injury; Augmenter of liver regeneration; Inflammation; Ischemia–reperfusion; Mitophagy; Reactive oxygen species

DOI:  https://doi.org/10.1007/s10495-022-01794-1
Mitochondrion. 2022 Nov 07. pii: S1567-7249(22)00088-5. [Epub ahead of print]

Tissue imaging reveals disruption of epithelial mitochondrial networks and loss of mitochondria-associated cytochrome-C in inflamed human and murine colon.

Andrew K Chojnacki, Saranya Navaneetha Krishnan, Humberto Jijon, Timothy E Shutt, Pina Colarusso, Derek M McKay.

  Mitochondrial dysfunction as defined by transcriptomic and proteomic analysis of biopsies or ultra-structure in transmission electron microscopy occurs in inflammatory bowel disease (IBD); however, mitochondrial dynamics in IBD have received minimal attention, with most investigations relying on cell-based in vitro models. We build on these studies by adapting the epithelial cell immunofluorescence workflow to imaging mitochondrial networks in normal and inflamed colonic tissue (i.e., murine di-nitrobenzene sulphonic acid (DNBS)-induced colitis, human ulcerative colitis). Using antibodies directed to TOMM20 (translocase of outer mitochondrial membrane 20) and cytochrome-C, we have translated the cell-based protocol for high-fidelity imaging to examine epithelial mitochondria networks in intact intestine. In epithelia of non-inflamed small or large intestinal tissue, the mitochondrial networks were dense and compact. This pattern was more pronounced in the basal region of the cell compared to that between the nucleus and apical surface facing the gut lumen. In comparison, mitochondrial networks in inflamed tissue displayed substantial loss of TOMM20+ staining. The remaining networks were less dense and fragmented, and contained isolated spherical mitochondrial fragments. The degree of mitochondrial network fragmentation mirrored the severity of inflammation, as assessed by blinded semi-quantitative scoring. As an indication of poor cell 'health' or viability, cytosolic cytochrome-C was observed in enterocytes with highly fragmented mitochondria. Thus, high-resolution and detailed visualization of mitochondrial networks in tissue is a feasible and valuable approach to assess disease, suited to characterizing mitochondrial abnormalities in tissue. We speculate that drugs that maintain a functional remodelling mitochondrial network and limit excess fragmentation could be a valuable addition to current therapies for IBD.

Keywords:  IBD; TOMM20; epithelium; in situ tissue imaging; mitochondrial dynamics

DOI:  https://doi.org/10.1016/j.mito.2022.10.004
J Biochem. 2022 Nov 08. pii: mvac092. [Epub ahead of print]

Ubiquitin-mediated mitochondrial regulation by MITOL/MARCHF5 at a glance.

Shun Nagashima, Naoki Ito, Isshin Shiiba, Hiroki Shimura, Shigeru Yanagi.

  Mitochondria are involved in various cellular processes, such as energy production, inflammatory responses, and cell death. Mitochondrial dysfunction is associated with many age-related diseases, including neurological disorders and heart failure. Mitochondrial quality is strictly maintained by mitochondrial dynamics linked to an adequate supply of phospholipids and other substances from the endoplasmic reticulum (ER). The outer mitochondrial membrane-localized E3 ubiquitin ligase MITOL/MARCHF5 is responsible for mitochondrial quality control through the regulation of mitochondrial dynamics, formation of mitochondria-ER contacts, and mitophagy. MITOL deficiency has been shown to impair mitochondrial function, cause an excessive inflammatory response, and increase vulnerability to stress, resulting in the exacerbation of the disease. In this study, we overview the ubiquitin-mediated regulation of mitochondrial function by MITOL and the relationship between MITOL and diseases.

Keywords:  MITOL/MARCHF5; mitochondria; mitochondria-ER contacts; mitochondrial dynamics; ubiquitin

DOI:  https://doi.org/10.1093/jb/mvac092
Nat Commun. 2022 Nov 07. 13(1): 6704

Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA.

Ayesha Sen, Sebastian Kallabis, Felix Gaedke, Christian Jüngst, Julia Boix, Julian Nüchel, Kanjanamas Maliphol, Julia Hofmann, Astrid C Schauss, Marcus Krüger, Rudolf J Wiesner, David Pla-Martín.

Understanding the mechanisms governing selective turnover of mutation-bearing mtDNA is fundamental to design therapeutic strategies against mtDNA diseases. Here, we show that specific mtDNA damage leads to an exacerbated mtDNA turnover, independent of canonical macroautophagy, but relying on lysosomal function and ATG5. Using proximity labeling and Twinkle as a nucleoid marker, we demonstrate that mtDNA damage induces membrane remodeling and endosomal recruitment in close proximity to mitochondrial nucleoid sub-compartments. Targeting of mitochondrial nucleoids is controlled by the ATAD3-SAMM50 axis, which is disrupted upon mtDNA damage. SAMM50 acts as a gatekeeper, influencing BAK clustering, controlling nucleoid release and facilitating transfer to endosomes. Here, VPS35 mediates maturation of early endosomes to late autophagy vesicles where degradation occurs. In addition, using a mouse model where mtDNA alterations cause impairment of muscle regeneration, we show that stimulation of lysosomal activity by rapamycin, selectively removes mtDNA deletions without affecting mtDNA copy number, ameliorating mitochondrial dysfunction. Taken together, our data demonstrates that upon mtDNA damage, mitochondrial nucleoids are eliminated outside the mitochondrial network through an endosomal-mitophagy pathway. With these results, we unveil the molecular players of a complex mechanism with multiple potential benefits to understand mtDNA related diseases, inherited, acquired or due to normal ageing.

DOI: https://doi.org/10.1038/s41467-022-34205-9
Redox Biol. 2022 Oct 13. pii: S2213-2317(22)00280-4. [Epub ahead of print]58 102508

SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia.

Stephen L Archer, Asish Dasgupta, Kuang-Hueih Chen, Danchen Wu, Kaushal Baid, John E Mamatis, Victoria Gonzalez, Austin Read, Rachel Et Bentley, Ashley Y Martin, Jeffrey D Mewburn, Kimberly J Dunham-Snary, Gerald A Evans, Gary Levy, Oliver Jones, Ruaa Al-Qazazi, Brooke Ring, Elahe Alizadeh, Charles Ct Hindmarch, Jenna Rossi, Patricia DA Lima, Darryl Falzarano, Arinjay Banerjee, Che C Colpitts.

  RATIONALE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 pneumonia. We hypothesize that SARS-CoV-2 causes alveolar injury and hypoxemia by damaging mitochondria in airway epithelial cells (AEC) and pulmonary artery smooth muscle cells (PASMC), triggering apoptosis and bioenergetic impairment, and impairing hypoxic pulmonary vasoconstriction (HPV), respectively.OBJECTIVES: We examined the effects of: A) human betacoronaviruses, SARS-CoV-2 and HCoV-OC43, and individual SARS-CoV-2 proteins on apoptosis, mitochondrial fission, and bioenergetics in AEC; and B) SARS-CoV-2 proteins and mouse hepatitis virus (MHV-1) infection on HPV.
METHODS: We used transcriptomic data to identify temporal changes in mitochondrial-relevant gene ontology (GO) pathways post-SARS-CoV-2 infection. We also transduced AECs with SARS-CoV-2 proteins (M, Nsp7 or Nsp9) and determined effects on mitochondrial permeability transition pore (mPTP) activity, relative membrane potential, apoptosis, mitochondrial fission, and oxygen consumption rates (OCR). In human PASMC, we assessed the effects of SARS-CoV-2 proteins on hypoxic increases in cytosolic calcium, an HPV proxy. In MHV-1 pneumonia, we assessed HPV via cardiac catheterization and apoptosis using the TUNEL assay.
RESULTS: SARS-CoV-2 regulated mitochondrial apoptosis, mitochondrial membrane permeabilization and electron transport chain (ETC) GO pathways within 2 hours of infection. SARS-CoV-2 downregulated ETC Complex I and ATP synthase genes, and upregulated apoptosis-inducing genes. SARS-CoV-2 and HCoV-OC43 upregulated and activated dynamin-related protein 1 (Drp1) and increased mitochondrial fission. SARS-CoV-2 and transduced SARS-CoV-2 proteins increased apoptosis inducing factor (AIF) expression and activated caspase 7, resulting in apoptosis. Coronaviruses also reduced OCR, decreased ETC Complex I activity and lowered ATP levels in AEC. M protein transduction also increased mPTP opening. In human PASMC, M and Nsp9 proteins inhibited HPV. In MHV-1 pneumonia, infected AEC displayed apoptosis and HPV was suppressed. BAY K8644, a calcium channel agonist, increased HPV and improved SpO2.
CONCLUSIONS: Coronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.

Keywords:  Apoptosis; Apoptosis inducing factor (AIF); Dynamin related protein 1 (Drp1); HCoV-OC43; Hypoxic pulmonary vasoconstriction; Mitochondrial fission; Mitochondrial permeability transition pore (mPTP); Murine hepatitis virus (MHV-1)

DOI:  https://doi.org/10.1016/j.redox.2022.102508
Biomedicines. 2022 Nov 10. pii: 2883. [Epub ahead of print]10(11):

Mitochondrial Transplantation Moderately Ameliorates Retinal Degeneration in Royal College of Surgeons Rats.

Shih-Fang Wu, Chih-Yao Lin, Rong-Kung Tsai, Yao-Tseng Wen, Feng-Huei Lin, Chia-Yu Chang, Ching-I Shen, Shinn-Zong Lin, Horng-Jyh Harn, Tzyy-Wen Chiou, Chin-San Liu, Yan-Ting Chen, Hong-Lin Su.

  Retinal pigmented epithelial (RPE) cells possess high mitochondria content for energy production, which is required for phagocytosis and vision cycle metabolism. The mitochondrial integrity in RPE cells helps the homeostasis of photoreceptor turnover and prevents retina aging and degeneration. Mitochondrial transplantation benefits the recovery of several acute inflammatory diseases, leading us to investigate the effects of mitochondrial transplantation on retina degeneration. Allogeneic mitochondria were isolated and delivered into the vitreous chamber in the Royal College of Surgeons (RCS) rats, which exhibit inherited and early-onset retina degeneration. The progress of retina degeneration was examined with optical coherence tomography (OCT) and visual evoked potential (VEP) to determine the retina thickness and integrity of afferent electrical signals from affected eyes, respectively. We found that mitochondria engraftment moderately attenuated the degeneration of retinal layers in RCS rats by histological examination. This result was consistent with the OCT measurement of retina thickness around the optic disc. The VEP analysis revealed that the peak one (N1) latency, representing the arriving time of electrical impulse from the retina to cortex, was substantially maintained as the normal value after the mitochondrial transplantation. This result suggests that the intra-vitreous transplanted mitochondria ameliorate the degeneration of photoreceptors in RCS rats and might be potential for clinical application.

Keywords:  macular degeneration; mitochondrial transplantation; retinal degeneration; retinitis pigmentosa

DOI:  https://doi.org/10.3390/biomedicines10112883
FASEB J. 2022 Dec;36(12): e22637

Mitochondrial dynamics, Leydig cell function, and age-related testosterone deficiency.

Samuel Garza, Liting Chen, Melanie Galano, Garett Cheung, Chantal Sottas, Lu Li, Yuchang Li, Barry R Zirkin, Vassilios Papadopoulos.

  The mitochondrial translocator protein (18 kDa; TSPO) is a high-affinity cholesterol-binding protein that is an integral component of the cholesterol trafficking scaffold responsible for determining the rate of cholesterol import into the mitochondria for steroid biosynthesis. Previous studies have shown that TSPO declines in aging Leydig cells (LCs) and that its decline is associated with depressed circulating testosterone levels in aging rats. However, TSPO's role in the mechanistic decline in LC function is not fully understood. To address the role of TSPO depletion in LC function, we first examined mitochondrial quality in Tspo knockout mouse tumor MA-10 nG1 LCs compared to wild-type MA-10 cells. Tspo deletion caused a disruption in mitochondrial function and membrane dynamics. Increasing mitochondrial fusion via treatment with the mitochondrial fusion promoter M1 or by optic atrophy 1 (OPA1) overexpression resulted in the restoration of mitochondrial function and mitochondrial morphology as well as in steroid formation in TSPO-depleted nG1 LCs. LCs isolated from aged rats form less testosterone than LCs isolated from young rats. Treatment of aging LCs with M1 improved mitochondrial function and increased androgen formation, suggesting that aging LC dysfunction may stem from compromised mitochondrial dynamics caused by the age-dependent LC TSPO decline. These results, taken together, suggest that maintaining or enhancing mitochondrial fusion may provide therapeutic strategies to maintain or restore testosterone levels with aging.

Keywords:  aging; bioenergetics; hypogonadism; mitochondrial fusion; optic atrophy 1; steroidogenesis; testosterone; translocator protein

DOI:  https://doi.org/10.1096/fj.202201026R
Elife. 2022 Nov 10. pii: e81033. [Epub ahead of print]11

Endosymbiotic selective pressure at the origin of eukaryotic cell biology.

Parth K Raval, Sriram G Garg, Sven B Gould.

  The dichotomy that separates prokaryotic from eukaryotic cells runs deep. The transition from pro- to eukaryote evolution is poorly understood due to a lack of reliable intermediate forms and definitions regarding the nature of the first host that could no longer be considered a prokaryote, the first eukaryotic common ancestor, FECA. The last eukaryotic common ancestor, LECA, was a complex cell that united all traits characterising eukaryotic biology including a mitochondrion. The role of the endosymbiotic organelle in this radical transition towards complex life forms is, however, sometimes questioned. In particular the discovery of the asgard archaea has stimulated discussions regarding the pre-endosymbiotic complexity of FECA. Here we review differences and similarities among models that view eukaryotic traits as isolated coincidental events in asgard archaeal evolution or, on the contrary, as a result of and in response to endosymbiosis. Inspecting eukaryotic traits from the perspective of the endosymbiont uncovers that eukaryotic cell biology can be explained as having evolved as a solution to housing a semi-autonomous organelle and why the addition of another endosymbiont, the plastid, added no extra compartments. Mitochondria provided the selective pressures for the origin (and continued maintenance) of eukaryotic cell complexity. Moreover, they also provided the energetic benefit throughout eukaryogenesis for evolving thousands of gene families unique to eukaryotes. Hence, a synthesis of the current data lets us conclude that traits such as the Golgi apparatus, the nucleus, autophagosomes, and meiosis and sex evolved as a response to the selective pressures an endosymbiont imposes.

Keywords:  FECA; LECA; cell biology; endomembrane system; endosymbiosis; eukaryogenesis; mitochondria

DOI:  https://doi.org/10.7554/eLife.81033
Elife. 2022 Nov 08. pii: e82206. [Epub ahead of print]11

Connexin 43 hemichannels regulate mitochondrial ATP generation, mobilization, and mitochondrial homeostasis against oxidative stress.

Jingruo Zhang, Manuel A Riquelme, Rui Hua, Francisca M Acosta, Sumin Gu, Jean X Jiang.

  Oxidative stress is a major risk factor that causes osteocyte cell death and bone loss. Prior studies primarily focus on the function of cell surface expressed Cx43 channels. Here, we reported a new role of mitochondrial Cx43 (mtCx43) and hemichannels (HCs) in modulating mitochondria homeostasis and function in bone osteocytes under oxidative stress. In murine long bone osteocyte-Y4 cells, the translocation of Cx43 to mitochondria was increased under H2O2-induced oxidative stress. H2O2 increased the mtCx43 level accompanied by elevated mtCx43 HC activity, determined by dye uptake assay. Cx43 knockdown (KD) by the CRISPR-Cas9 lentivirus system resulted in impairment of mitochondrial function, primarily manifested as decreased ATP production. Cx43 KD had reduced intracellular reactive oxidative species levels and mitochondrial membrane potential. Additionally, live-cell imaging results demonstrated that the proton flux was dependent on mtCx43 HCs because its activity was specifically inhibited by an antibody targeting Cx43 C-terminus. The co-localization and interaction of mtCx43 and ATP synthase subunit F (ATP5J2) were confirmed by Förster resonance energy transfer and a protein pull-down assay. Together, our study suggests that mtCx43 HCs regulate mitochondrial ATP generation by mediating K+, H+, and ATP transfer across the mitochondrial inner membrane and the interaction with mitochondrial ATP synthase, contributing to the maintenance of mitochondrial redox levels in response to oxidative stress.

Keywords:  ATP synthase; cell biology; connexin 43; mouse; osteocytes; oxidative stress; proton

DOI:  https://doi.org/10.7554/eLife.82206