Entry Name Mitophagy - animal
Description Mitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process called reactive oxidative species (ROS) lead to mitochondrial dysfunction. If the damage is too excessive to be repaired, such mitochondria are selectively recognized and targeted for degradation by a specific mode of autophagy, termed mitophagy. The loss of the mitochondrial membrane potential can induce mitophagy, involving the kinase PINK1 and the E3 ligase Parkin. PINK1 serves as the sensor for the mitochondrial depolarization and recruits Parkin, followed by ubiquitin-dependent recruitment of mitophagy receptors. There are also several PINK1/Parkin-independent mitophagy pathways, in which a group of LIR-containing receptors are required in response to different stimuli. Mitophagy contributes to the maintenance of a healthy mitochondrial network and the prevention of programmed cell death.
Class Cellular Processes; Transport and catabolismBRITE hierarchy
Pathway map Other DBs Orthology K02927 RP-L40e, RPL40, UBA52; ubiquitin-large subunit ribosomal protein L40e
K02977 RP-S27Ae, RPS27A, UBA80; ubiquitin-small subunit ribosomal protein S27Ae
K03115 CSNK2B; casein kinase II subunit beta
K03237 EIF2S1; translation initiation factor 2 subunit 1
K04374 ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04448 JUN; transcription factor AP-1
K04451 TP53, P53; tumor protein p53
K04570 BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04684 SP1; transcription factor Sp1
K04735 RELA; transcription factor p65
K06030 MFN2, FZO1; mitofusin 2 [EC:3.6.5.-]
K07277 SAM50, TOB55, bamA; outer membrane protein insertion porin family
K07827 KRAS, KRAS2; GTPase KRas
K07829 RRAS; Ras-related protein R-Ras
K07830 RRAS2, TC21; Ras-related protein R-Ras2
K07831 MRAS; Ras-related protein M-Ras
K07870 RHOT1, ARHT1; mitochondrial Rho GTPase 1 [EC:3.6.5.-]
K07871 RHOT2, ARHT2; mitochondrial Rho GTPase 2 [EC:3.6.5.-]
K07887 RAB5A; Ras-related protein Rab-5A
K07888 RAB5B; Ras-related protein Rab-5B
K07889 RAB5C; Ras-related protein Rab-5C
K07897 RAB7A; Ras-related protein Rab-7A
K07898 RAB7B; Ras-related protein Rab-7B
K08268 HIF1A; hypoxia-inducible factor 1 alpha
K08334 BECN, VPS30, ATG6; beclin
K08341 GABARAP, ATG8, LC3; GABA(A) receptor-associated protein
K08860 EIF2AK3, PERK; eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1 ]
K09105 TFE3; transcription factor E3
K09408 FOXO3; forkhead box protein O3
K09455 MITF; microphthalmia-associated transcription factor
K10435 MAP1LC; microtubule-associated protein 1 light chain
K10592 HUWE1, MULE, ARF-BP1, TOM1; E3 ubiquitin-protein ligase HUWE1 [EC:2.3.2.26 ]
K11518 TOM40; mitochondrial import receptor subunit TOM40
K12653 NLRX1; NLR family member X1
K13525 VCP, CDC48; transitional endoplasmic reticulum ATPase
K15464 BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3
K15465 BNIP3L; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like
K15485 BCL2L13, BCL-RAMBO; Bcl-2-like protein 13
K15590 TFEB; transcription factor EB
K15637 PGAM5; serine/threonine-protein phosphatase PGAM5 [EC:3.1.3.16 ]
K17454 E2F1; transcription factor E2F1
K17768 TOM70; mitochondrial import receptor subunit TOM70
K17770 TOM20; mitochondrial import receptor subunit TOM20
K17771 TOM7; mitochondrial import receptor subunit TOM7
K17907 ATG9; autophagy-related protein 9
K17969 FIS1, TTC11, MDV2; mitochondrial fission 1 protein
K17985 AMBRA1; activating molecule in BECN1-regulated autophagy protein 1
K17986 FUNDC1; FUN14 domain-containing protein 1
K17987 NBR1; next to BRCA1 gene 1 protein
K19945 TBC1D17; TBC1 domain family member 17
K20131 RABGEF1; Rab5 GDP/GTP exchange factor
K20168 TBC1D15; TBC1 domain family member 15
K20195 MON1; vacuolar fusion protein MON1
K21347 TAX1BP1; Tax1-binding protein 1
K21348 CALCOCO2, NDP52; calcium-binding and coiled-coil domain-containing protein 2
K21356 MFN1; mitofusin 1 [EC:3.6.5.-]
K21361 CITED2; Cbp/p300-interacting transactivator 2
K27045 CCZ1; vacuolar fusion protein CCZ1, animal type
Compound Reference Authors Pickrell AM, Youle RJ
Title The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease.
Journal Reference Authors Durcan TM, Fon EA
Title The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications.
Journal Reference Authors Shirihai OS, Song M, Dorn GW 2nd
Title How mitochondrial dynamism orchestrates mitophagy.
Journal Reference Authors Hamacher-Brady A, Brady NR
Title Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy.
Journal Reference Authors Yamano K, Matsuda N, Tanaka K
Title The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation.
Journal Reference Authors Yamaguchi O, Murakawa T, Nishida K, Otsu K
Title Receptor-mediated mitophagy.
Journal Reference Authors Roberts RF, Tang MY, Fon EA, Durcan TM
Title Defending the mitochondria: The pathways of mitophagy and mitochondrial-derived vesicles.
Journal Reference Authors Arena G, Valente EM
Title PINK1 in the limelight: multiple functions of an eclectic protein in human health and disease.
Journal Related
