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Cited by 291Mitochondrial Function and PathologyATP Synthase and ATPases ResearchAutophagy in Disease and Therapy

MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture

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Friedman, Jonathan R, Mourier, Arnaud, Yamada, Justin, McCaffery, J Michael, Nunnari, Jodi·2015·eLife
DOI 10.7554/elife.07739PMC PMC4434539
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Abstract

The conserved MICOS complex functions as a primary determinant of mitochondrial inner membrane structure. We address the organization and functional roles of MICOS and identify two independent MICOS subcomplexes: Mic27/Mic10/Mic12, whose assembly is dependent on respiratory complexes and the mitochondrial lipid cardiolipin, and Mic60/Mic19, which assembles independent of these factors. Our data suggest that MICOS subcomplexes independently localize to cristae junctions and are connected via Mic19, which functions to regulate subcomplex distribution, and thus, potentially also cristae junction copy number. MICOS subunits have non-redundant functions as the absence of both MICOS subcomplexes results in more severe morphological and respiratory growth defects than deletion of single MICOS subunits or subcomplexes. Mitochondrial defects resulting from MICOS loss are caused by misdistribution of respiratory complexes in the inner membrane. Together, our data are consistent with a model where MICOS, mitochondrial lipids and respiratory complexes coordinately build a functional and correctly shaped mitochondrial inner membrane.

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  • ApoE4 also affects respiratory complex formation.

    “In concert with mitochondrial proteases, which respond to altered mitochondrial protein stoichiometry [107], apoE4 also affects respiratory complex formation [108].”

    From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [108]

    The Results and Discussion passages address MICOS, respiratory complexes, and mitochondrial architecture, but do not address apoE4. Searches for “apoE4,” “apolipoprotein E4,” and its effect on respiratory complex formation found no supporting passage in our copy. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Friedman, J. R., Mourier, A., Yamada, J., McCaffery, J. M., & Nunnari, J.
Affiliations
  • University of California, Davis (US)
  • Max Planck Institute for Biology of Ageing (DE)
  • Johns Hopkins University (US)
Corresponding author
Nunnari, Jodi
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2015-04-28
Volume
4
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.07739
PMC
PMC4434539
OpenAlex
W2039907011
Cited by
291
References
3
Citations by year
2026: 30 · 2025: 24 · 2024: 22 · 2023: 20 · 2022: 30 · 2021: 31 · 2020: 26 · 2019: 30 · 2018: 12 · 2017: 32 · 2016: 28 · 2015: 6
FWCI
10.26
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (NIH) (R01GM062942, R01GM097432, R01GM106019)
  • Jane Coffin Childs Memorial Fund for Medical Research (fellowship)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
MICOS complex, cardiolipin, respiratory chain complexes, mitochondrial morphology
MeSH terms
Cardiolipins, Membrane Proteins, Mitochondria, Protein Binding, Recombinant Proteins, Recombination, Genetic, Saccharomyces cerevisiae, Mitochondrial Proteins, Saccharomyces cerevisiae Proteins, Electron Transport Complex II, Electron Transport Complex I, Mitochondrial Membranes

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