Mitochondrial protein import: from proteomics to functional mechanisms
Abstract
Mitochondria contain approximately 1,000 different proteins, most of which are imported from the cytosol. Two import pathways that direct proteins into the mitochondrial inner membrane and matrix have been known for many years. The identification of numerous new transport components in recent proteomic studies has led to novel mechanistic insight into these pathways and the discovery of new import pathways into the outer membrane and intermembrane space. Protein translocases do not function as independent units but are integrated into dynamic networks and are connected to machineries that function in bioenergetics, mitochondrial morphology and coupling to the endoplasmic reticulum.
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MOMP eventually leads to the dissipation of the mitochondrial transmembrane potential (Δψm)-mostly as a consequence of the respiratory impairment imposed by the loss of CYCS-and hence to the cessation of Δψm-dependent mitochondrial functions (including ATP synthesis and some forms of protein import).
“Of note, MOMP eventually leads to the dissipation of the mitochondrial transmembrane potential (Δψm)—mostly as a consequence of the respiratory impairment imposed by the loss of CYCS—and hence to the cessation of Δψm-dependent mitochondrial functions (including ATP synthesis and some forms of protein import) [200–203].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [203]
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Biogenesis of mitochondrial outer membrane proteins
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Alternative function for the mitochondrial SAM complex in biogenesis of α-helical TOM proteins
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Cryo-Electron Microscopy Structure of a Yeast Mitochondrial Preprotein Translocase
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Mdm10 as a dynamic constituent of the TOB/SAM complex directs coordinated assembly of Tom40
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Self-citationThe Tim21 binding domain connects the preprotein translocases of both mitochondrial membranes
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Self-citationTranslation-coupled Translocation of Yeast Fumarase into Mitochondria in Vivo
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Systematic Identification of Mitochondrial Proteins by LC−MS/MS
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Dual Targeting of Nfs1 and Discovery of Its Novel Processing Enzyme, Icp55
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Expanded protein information at SGD: new pages and proteome browser
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The Assembly Pathway of the Mitochondrial Carrier Translocase Involves Four Preprotein Translocases
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Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Mitochondria: In Sickness and in Health
Nunnari, J., & Suomalainen, A. (2012) · Cell · doi:10.1016/j.cell.2012.02.035 · Cited by 3,479 · see citing works
Mitochondrial form and function
Friedman, J. R., & Nunnari, J. (2014) · Nature · doi:10.1038/nature12985 · Cited by 1,803 · see citing works
Pharmacological approaches to restore mitochondrial function
Andreux, P. A., Houtkooper, R. H., & Auwerx, J. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4023 · Cited by 383 · see citing works
The Ubiquitin-Proteasome System Regulates Mitochondrial Intermembrane Space Proteins
Bragoszewski, P., Gornicka, A., Sztolsztener, M. E., & Chacinska, A. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01579-12 · Cited by 149 · see citing works
PNPASE and RNA trafficking into mitochondria
Wang, G., Shimada, E., Koehler, C. M., & Teitell, M. A. (2012) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2011.10.001 · Cited by 84 · see citing works
“been well characterized [1-4], the pathways importing RNAs into mammalian mitochondria, and the functions of imported RNAs, are just being discovered.”
BackgroundRensvold, J. W., Ong, S.-E., Jeevananthan, A., Carr, S. A., Mootha, V. K., & Pagliarini, D. J. (2013) · Cell Reports · doi:10.1016/j.celrep.2012.11.029 · Cited by 82 · see citing works
Mitochondria-cytosol-nucleus crosstalk: learning from Saccharomyces cerevisiae
Guaragnella, N., Coyne, L. P., Chen, X. J., & Giannattasio, S. (2018) · FEMS Yeast Research · doi:10.1093/femsyr/foy088 · Cited by 72 · see citing works
Mitochondrial health, the epigenome and healthspan
Aon, M. A., Cortassa, S., Juhaszova, M., & Sollott, S. J. (2016) · Clinical Science · doi:10.1042/cs20160002 · Cited by 66 · see citing works
- Authors
- Schmidt, O., Pfanner, N., & Meisinger, C.
- Affiliations
- University of Freiburg (DE)
- Corresponding author
- Pfanner, Nikolaus
- Meisinger, Chris
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2010-09
- Volume
- 11
- Issue
- 9
- Pages
- 655-667
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2087864393
- Cited by
- 717
- References
- 134
- Citations by year
- 2026: 24 · 2025: 41 · 2024: 46 · 2023: 41 · 2022: 54 · 2021: 44 · 2020: 37 · 2019: 24 · 2018: 41 · 2017: 47 · 2016: 46 · 2015: 60 · 2014: 48 · 2013: 49 · 2012: 66
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- 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 import, protein translocase, TOM complex, mitochondrial outer membrane, intermembrane space, inner mitochondrial membrane, mitochondrial matrix, mitochondrial morphology, bioenergetics
- MeSH terms
- Animals, Humans, Protein Transport, Mitochondrial Proteins, Mitochondrial Membrane Transport Proteins, Proteomics, Mitochondrial Membranes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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