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Cited by 73Mitochondrial Function and PathologyGenetics, Aging, and Longevity in Model OrganismsAutophagy in Disease and Therapy

Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain

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Krishna, Shefali, Arrojo e Drigo, Rafael, Capitanio, Juliana S., Ramachandra, Ranjan, Ellisman, Mark, Hetzer, Martin W.·2021·Developmental Cell
DOI 10.1016/j.devcel.2021.10.008PMC PMC8664086
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Abstract

In order to combat molecular damage, most cellular proteins undergo rapid turnover. We have previously identified large nuclear protein assemblies that can persist for years in post-mitotic tissues and are subject to age-related decline. Here, we report that mitochondria can be long lived in the mouse brain and reveal that specific mitochondrial proteins have half-lives longer than the average proteome. These mitochondrial long-lived proteins (mitoLLPs) are core components of the electron transport chain (ETC) and display increased longevity in respiratory supercomplexes. We find that COX7C, a mitoLLP that forms a stable contact site between complexes I and IV, is required for complex IV and supercomplex assembly. Remarkably, even upon depletion of COX7C transcripts, ETC function is maintained for days, effectively uncoupling mitochondrial function from ongoing transcription of its mitoLLPs. Our results suggest that modulating protein longevity within the ETC is critical for mitochondrial proteome maintenance and the robustness of mitochondrial function.

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  • The half-life of mitochondria is a couple of weeks in several cell types.

    “The half-life of mitochondria is known to be a couple of weeks in several cell types,20”

    From ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes (2023) · cites this paper as [20]

    The Results section reports mitochondrial-protein half-lives in two cell types: 7 days in neurons and 5.5 days in myotubes. That supports the broader point that mitochondrial turnover varies by cell type, but it does not establish a roughly two-week half-life for mitochondria themselves; the paper says the lifespan of individual mitochondria is unknown. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Krishna, S., Arrojo e Drigo, R., Capitanio, J. S., Ramachandra, R., Ellisman, M., & Hetzer, M. W.
Affiliations
  • Salk Institute for Biological Studies (US)
  • University of California San Diego (US)
Corresponding author
Hetzer, Martin W.
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2021-11
Volume
56
Issue
21
Pages
2952-2965.e9
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2021.10.008
PMC
PMC8664086
OpenAlex
W3203222983
Cited by
73
References
9
Citations by year
2026: 14 · 2025: 22 · 2024: 19 · 2023: 8 · 2022: 9 · 2021: 1
FWCI
2.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • W. M. Keck Foundation
  • Compton Foundation
  • Leona M. and Harry B. Helmsley Charitable Trust
  • National Science Foundation
  • NOMIS Stiftung
  • National Cancer Institute (P30 014195)
  • National Institutes of Health (R01 NS096786)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
long-lived proteins, mitochondrial proteins, protein stability, electron transport chain, respiratory supercomplexes, post-transcriptional regulation, brain mitochondria, age-related decline
MeSH terms
Animals, Electron Transport Complex IV, Electron Transport, Mitochondria, Oxidative Phosphorylation, Mitochondrial Proteins, Electron Transport Complex I, Mitochondrial Membranes, Mice

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