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Cited by 250Mitochondrial Function and PathologyATP Synthase and ATPases ResearchAutophagy in Disease and Therapy

MITRAC Links Mitochondrial Protein Translocation to Respiratory-Chain Assembly and Translational Regulation

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Mick, David U., Dennerlein, Sven, Wiese, Heike, Reinhold, Robert, Pacheu-Grau, David, Lorenzi, Isotta, Sasarman, Florin, Weraarpachai, Woranontee +3 more·2012·Cell
DOI 10.1016/j.cell.2012.11.053
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Abstract

Mitochondrial respiratory-chain complexes assemble from subunits of dual genetic origin assisted by specialized assembly factors. Whereas core subunits are translated on mitochondrial ribosomes, others are imported after cytosolic translation. How imported subunits are ushered to assembly intermediates containing mitochondria-encoded subunits is unresolved. Here, we report a comprehensive dissection of early cytochrome c oxidase assembly intermediates containing proteins required for normal mitochondrial translation and reveal assembly factors promoting biogenesis of human respiratory-chain complexes. We find that TIM21, a subunit of the inner-membrane presequence translocase, is also present in the major assembly intermediates containing newly mitochondria-synthesized and imported respiratory-chain subunits, which we term MITRAC complexes. Human TIM21 is dispensable for protein import but required for integration of early-assembling, presequence-containing subunits into respiratory-chain intermediates. We establish an unexpected molecular link between the TIM23 transport machinery and assembly of respiratory-chain complexes that regulate mitochondrial protein synthesis in response to their assembly state.

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  • COX1 depletion results in defective assembly, and delivery of nuclear-encoded subunits reduces COX1 levels and also disrupts assembly.

    “COX1 depletion results in defective assembly, and delivery of nuclear-encoded subunits reduces COX1 levels and also disrupts assembly [82–87].”

    From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [84]

    The Results (page unavailable) report that MITRAC12 depletion reduces COX1 synthesis and the amount of newly synthesized COX1 in mature cytochrome c oxidase, supporting a link between COX1 loss and impaired assembly. They also show that TIM21 promotes assembly of an imported nuclear-encoded subunit. But the paper does not show that delivery of those subunits reduces COX1 levels; its Discussion describes reduced COX1 translation when the supply of imported subunits is limited, in yeast. (LLM, conf=0.84)

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Authors
Mick, D. U., Dennerlein, S., Wiese, H., Reinhold, R., Pacheu-Grau, D., Lorenzi, I., Sasarman, F., Weraarpachai, W., Shoubridge, E. A., Warscheid, B., & Rehling, P.
Affiliations
  • University of Göttingen (DE)
  • University of Freiburg (DE)
  • Montreal Neurological Institute and Hospital (CA)
  • Max Planck Institute for Biophysical Chemistry (DE)
Corresponding author
Rehling, Peter
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2012-12
Volume
151
Issue
7
Pages
1528-1541
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2012.11.053
OpenAlex
W2107439917
Cited by
250
References
1
Citations by year
2026: 23 · 2025: 13 · 2024: 19 · 2023: 29 · 2022: 17 · 2021: 20 · 2020: 22 · 2019: 14 · 2018: 20 · 2017: 15 · 2016: 19 · 2015: 11 · 2014: 16 · 2013: 12
FWCI
4.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • GRO (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • Deutsche Forschungsgemeinschaft
  • Canadian Institutes of Health Research
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
mitochondrial protein translocation, cytochrome c oxidase, mitochondrial protein import, mitochondrial translation, assembly intermediates, mitochondrial biogenesis, translational regulation
MeSH terms
Mitochondrial Precursor Protein Import Complex Proteins, Electron Transport Complex IV, Cytosol, Humans, Membrane Proteins, Mitochondria, Protein Biosynthesis, Mitochondrial Proteins, Membrane Transport Proteins, Mitochondrial Membrane Transport Proteins, Cyclooxygenase 1

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