The Oxidation Status of Mic19 Regulates MICOS Assembly

Sakowska, Paulina; Jans, Daniel C.; Mohanraj, Karthik Ganesh; Riedel, Dietmar; Jakobs, Stefan; Chacińska, Agnieszka

doi:10.1128/mcb.00578-15

Cited by 47 publications

(52 citation statements)

References 60 publications

(120 reference statements)

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“…8 D). Overall, these results are consistent with previous findings showing that MIC19 is a substrate of the AIF-Mia40-Erv1 intramitochondrial translocation system (Sakowska et al, 2015;Darshi et al, 2012).…”

Section: Daif Regulates Intramitochondrial Localization Of the Drosopsupporting

confidence: 93%

An antibody toolbox to track complex I assembly defines AIF’s mitochondrial function

Murari

Rhooms

Goparaju

et al. 2020

Journal of Cell Biology

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An ability to comprehensively track the assembly intermediates (AIs) of complex I (CI) biogenesis in Drosophila will enable the characterization of the precise mechanism(s) by which various CI regulators modulate CI assembly. Accordingly, we generated 21 novel antibodies to various mitochondrial proteins and used this resource to characterize the mechanism by which apoptosis-inducing factor (AIF) regulates CI biogenesis by tracking the AI profile observed when AIF expression is impaired. We find that when the AIF–Mia40 translocation complex is disrupted, the part of CI that transfers electrons to ubiquinone is synthesized but fails to progress in the CI biosynthetic pathway. This is associated with a reduction in intramitochondrial accumulation of the Mia40 substrate, MIC19. Importantly, knockdown of either MIC19 or MIC60, components of the mitochondrial contact site and cristae organizing system (MICOS), fully recapitulates the AI profile observed when AIF is inhibited. Thus, AIF’s effect on CI assembly is principally due to compromised intramitochondrial transport of the MICOS complex.

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Section: Daif Regulates Intramitochondrial Localization Of the Drosopsupporting

confidence: 93%

An antibody toolbox to track complex I assembly defines AIF’s mitochondrial function

Murari

Rhooms

Goparaju

et al. 2020

Journal of Cell Biology

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“…Whereas the mitochondrial import of the precursors of Mic60, Mic10 and further MICOS subunits requires an inner membrane potential, the precursor of Mic19 is imported in a membrane potential‐independent manner. Instead, like other disulphide‐containing CHCH proteins, Mic19 is imported into the intermembrane space via the mitochondrial import and assembly (MIA) pathway that couples import to the introduction of disulphide bonds . Interestingly, the biogenesis of Mic19 additionally depends on amino‐terminal myristoylation that mediates binding of the precursor to the TOM complex .…”

Section: The Mitochondrial Contact Site and Cristae Organizing Systemmentioning

confidence: 99%

Shaping the mitochondrial inner membrane in health and disease

et al. 2020

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Colina-Tenorio L, Horten P, Pfanner N, Rampelt H (University of Freiburg, Freiburg, Germany). Shaping the mitochondrial inner membrane in health and disease (Review Symposium). J Intern Med 2020; 287: 645-664.Mitochondria play central roles in cellular energetics, metabolism and signalling. Efficient respiration, mitochondrial quality control, apoptosis and inheritance of mitochondrial DNA depend on the proper architecture of the mitochondrial membranes and a dynamic remodelling of inner membrane cristae. Defects in mitochondrial architecture can result in severe human diseases affecting predominantly the nervous system and the heart. Inner membrane morphology is generated and maintained in particular by the mitochondrial contact site and cristae organizing system (MICOS), the F 1 F o -ATP synthase, the fusion protein OPA1/Mgm1 and the nonbilayer-forming phospholipids cardiolipin and phosphatidylethanolamine. These protein complexes and phospholipids are embedded in a network of functional interactions. They communicate with each other and additional factors, enabling them to balance different aspects of cristae biogenesis and to dynamically remodel the inner mitochondrial membrane. Genetic alterations disturbing these membrane-shaping factors can lead to human pathologies including fatal encephalopathy, dominant optic atrophy, Leigh syndrome, Parkinson's disease and Barth syndrome.

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“…Next to the central role of Mic60 it became clear that Mic10, which contains unique GXGXGXG motifs, can homooligomerize into a large subcomplex and is able to alter membrane curvature independent of other MICOS subunits 42 45 . Mic19 (Mic25 in metazoan) appears to be a regulatory subunit that is peripherally attached to the inner membrane and was proposed to be a redox-sensor of the MICOS complex 46 . Mic12, or its putative mammalian paralogue Mic13/Qil1, is required to stabilize the full MICOS complex by holding two subcomplexes, Mic60-Mic19 and Mic10-Mic12/Mic13-Mic26-Mic27, together 27 28 42 47 48 49 .…”

Section: Introductionmentioning

confidence: 99%

Cristae architecture is determined by an interplay of the MICOS complex and the F1Fo ATP synthase via Mic27 and Mic10

Eydt¹,

Davies²,

Behrendt³

et al. 2017

Microb Cell

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The inner boundary and the cristae membrane are connected by pore-like structures termed crista junctions (CJs). The MICOS complex is required for CJ formation and enriched at CJs. Here, we address the roles of the MICOS subunits Mic27 and Mic10. We observe a positive genetic interaction between Mic27 and Mic60 and deletion of Mic27 results in impaired formation of CJs and altered cristae membrane curvature. Mic27 acts in an antagonistic manner to Mic60 as it promotes oligomerization of the F1FO-ATP synthase and partially restores CJ formation in cells lacking Mic60. Mic10 impairs oligomerization of the F1FO-ATP synthase similar to Mic60. Applying complexome profiling, we observed that deletion of Mic27 destabilizes the MICOS complex but does not impair formation of a high molecular weight Mic10 subcomplex. Moreover, this Mic10 subcomplex comigrates with the dimeric F1FO-ATP synthase in a Mic27-independent manner. Further, we observed a chemical crosslink of Mic10 to Mic27 and of Mic10 to the F1FO-ATP synthase subunit e. We corroborate the physical interaction of the MICOS complex and the F1FO-ATP synthase. We propose a model in which part of the F1FO-ATP synthase is linked to the MICOS complex via Mic10 and Mic27 and by that is regulating CJ formation.

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The Oxidation Status of Mic19 Regulates MICOS Assembly

Cited by 47 publications

References 60 publications

An antibody toolbox to track complex I assembly defines AIF’s mitochondrial function

An antibody toolbox to track complex I assembly defines AIF’s mitochondrial function

Shaping the mitochondrial inner membrane in health and disease

Cristae architecture is determined by an interplay of the MICOS complex and the F1Fo ATP synthase via Mic27 and Mic10

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