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PINK1-PRKN Mediated Mitophagy
Stable Identifier
R-HSA-5205685
Type
Pathway
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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Autophagy (Homo sapiens)
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Selective autophagy (Homo sapiens)
Mitophagy (Homo sapiens)
PINK1-PRKN Mediated Mitophagy (Homo sapiens)
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This is the process of selective removal of damaged mitochondria by autophagosomes and subsequent catabolism by lysosomes. In healthy mitochondria, PINK1 is imported to the inner mitochondrial membrane, presumably through the TOM/TIM complex. The TIM complex associated protease, mitochondrial MPP, cleaves PINK1 mitochondrial targeting sequence (MTS). PINK1 may be cleaved by the inner membrane presenilin associated rhomboid like protease (PARL) and ultimately proteolytically degraded. Loss of membrane potential in damaged mitochondria prevents the import of the PTEN induced putative kinase 1 (PINK1) which accumulates in the defective mitochondria triggering the recruitment of the E3 ubiquitin protein ligase (Parkin). Once on the mitochondria, Parkin promotes the ubiquitination of mitochondrial substrates embedded in the OMM such as the mitofusin Mitochondrial Assembly Regulatory Factor (MARF), mitofusin 1 and 2 (Mfn1, 2) and the Voltage Dependent Anion Channel 1 (VDAC1). After the ubiquitination events, the cargo receptors such as p62 and OPTN are recruited to mitochondria, binding the Parkin ubiquitinated substrates, linking the ubiquitinated substrates to the Microtubule associated protein Autophagy marker Light Chain 3 (LC3). Targeting the entire mitochondria for autophagic degradation. The recruitment of LC3 complexes with the autophagosome membrane and the AuTophaGy proteins 5 12 (Atg5 Atg12) complex. The mitochondria is engulfed after the isolation membrane grows to a sufficient size to engulf the mitochondria. Once autophagic vesicle formation is complete, vesicle fusion with lysosomes occurs to form autophagolysosomes in which the lysosomal hydrolases (cathepsins and lipases) degrade the intra autophagosomal content. Cathepsin also degrades LC3 on the intra autophagosomal surface of the autophagic vesicle.
Literature References
PubMed ID
Title
Journal
Year
21179058
Mechanisms of mitophagy
Narendra, DP
,
Youle, RJ
Nat. Rev. Mol. Cell Biol.
2011
Participants
Events
Pink1 is recruited from the cytoplasm to the mitochondria
(Homo sapiens)
Pink1 is cleaved on healthy mitochondria
(Homo sapiens)
Uncleaved Pink1 accumulates in damaged mitochondria
(Homo sapiens)
Pink1 recruits Parkin to the outer mitochondrial membrane.
(Homo sapiens)
Parkin promotes the ubiquitination of mitochondrial substrates
(Homo sapiens)
p62 binds ubiquitinated mitochondrial substrates
(Homo sapiens)
p62 links damaged mitochondria to LC3
(Homo sapiens)
LC3 binds the autophagosome membrane Atg5-Atg12 complex
(Homo sapiens)
Participates
as an event of
Mitophagy (Homo sapiens)
Event Information
Go Biological Process
macroautophagy (0016236)
Orthologous Events
PINK1-PRKN Mediated Mitophagy (Bos taurus)
PINK1-PRKN Mediated Mitophagy (Caenorhabditis elegans)
PINK1-PRKN Mediated Mitophagy (Canis familiaris)
PINK1-PRKN Mediated Mitophagy (Danio rerio)
PINK1-PRKN Mediated Mitophagy (Drosophila melanogaster)
PINK1-PRKN Mediated Mitophagy (Gallus gallus)
PINK1-PRKN Mediated Mitophagy (Mus musculus)
PINK1-PRKN Mediated Mitophagy (Plasmodium falciparum)
PINK1-PRKN Mediated Mitophagy (Rattus norvegicus)
PINK1-PRKN Mediated Mitophagy (Sus scrofa)
PINK1-PRKN Mediated Mitophagy (Xenopus tropicalis)
Authored
Gillespie, ME (2013-11-21)
Reviewed
Chauss, D (2015-09-01)
Kantorow, M (2015-09-01)
Created
Gillespie, ME (2013-12-05)
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