The role of the individual TOM subunits in the association of PINK1 with depolarized mitochondria
Open accessAbstract
Mitochondria dysfunction is involved in the pathomechanism of many illnesses including Parkinson’s disease. PINK1, which is mutated in some cases of familial Parkinsonism, is a key component in the degradation of damaged mitochondria by mitophagy. The accumulation of PINK1 on the mitochondrial outer membrane (MOM) of compromised organelles is crucial for the induction of mitophagy, but the molecular mechanism of this process is still unresolved. Here, we investigate the association of PINK1 with the TOM complex. We demonstrate that PINK1 heavily relies on the import receptor TOM70 for its association with mitochondria and directly interacts with this receptor. The structural protein TOM7 appears to play only a moderate role in PINK1 association with the TOM complex, probably due to its role in stabilizing this complex. PINK1 requires the TOM40 pore lumen for its stable interaction with the TOM complex and apparently remains there during its further association with the MOM. Overall, this study provides new insights on the role of the individual TOM subunits in the association of PINK1 with the MOM of depolarized mitochondria. Key messages: TOM70 is the main receptor for the import of PINK1 into mitochondria. TOM20 plays only a minor role in PINK1 recognition at the organellar outer membrane. PINK1 association with the TOM complex is reduced upon knock-down of TOM7. The lumen of the TOM pore is crucial for PINK1 association with the outer membrane. TcPINK1 blocks the TOM pore in depolarized mitochondria.
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Mitochondrial depolarization stabilizes PINK1 by arresting its import at the TOM complex, preventing turnover and allowing accumulation of full-length, dimerized PINK1 on the outer mitochondrial membrane.
“Current models suggest that mitochondrial depolarization stabilizes PINK1 by arresting its import at the TOM complex, thereby preventing turnover and allowing accumulation of full-length, dimerized PINK1 on the outer mitochondrial membrane [59–62].”
From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [60]
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- Authors
- Maruszczak, K. K., Jung, M., Rasool, S., Trempe, J.-F., & Rapaport, D.
- Affiliations
- University of Tübingen (DE)
- Saarland University (DE)
- McGill University (CA)
- Corresponding author
- Rapaport, Doron
- Venue
- Journal of Molecular Medicine
- Published
- 2022-04-07
- Volume
- 100
- Issue
- 5
- Pages
- 747-762
- ISSN
- 0946-2716 (ISSN-L)
- 1432-1440
- PMC
- PMC9110474
- OpenAlex
- W4226243460
- Cited by
- 29
- References
- 30
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 6 · 2023: 6
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Universitätsbibliothek Tübingen
- Funders
- Deutsche Forschungsgemeinschaft (RTG2364, CRC 894)
- Eberhard Karls Universität Tübingen
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- PINK1, TOM complex, Tom70, Tom40, Tom20, mitochondrial depolarization, mitophagy, mitochondrial outer membrane, mitochondrial protein import, Parkinson's disease
- MeSH terms
- Mitochondrial Precursor Protein Import Complex Proteins, Carrier Proteins, Mitochondria, Protein Kinases, Mitochondrial Membrane Transport Proteins, Mitophagy
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