KEGG   PATHWAY: ko04137
ko04137                     Pathway                                
Mitophagy - animal
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.
Cellular Processes; Transport and catabolism
Pathway map
ko04137  Mitophagy - animal

Other DBs
GO: 0000422
K17985  activating molecule in BECN1-regulated autophagy protein 1
K05688  PTEN induced putative kinase 1 [EC:]
K17771  mitochondrial import receptor subunit TOM7
K11518  mitochondrial import receptor subunit TOM40
K17770  mitochondrial import receptor subunit TOM20
K17768  mitochondrial import receptor subunit TOM70
K04556  parkin [EC:]
K10660  E3 ubiquitin-protein ligase MARCH5 [EC:]
K03173  TNF receptor-associated factor 2 [EC:]
K04678  E3 ubiquitin ligase SMURF1/2 [EC:]
K10636  E3 ubiquitin-protein ligase AMFR [EC:]
K15688  E3 ubiquitin-protein ligase MUL1 [EC:]
K10592  E3 ubiquitin-protein ligase HUWE1 [EC:]
K04506  E3 ubiquitin-protein ligase SIAH1 [EC:]
K11968  ariadne-1 [EC:]
K21356  mitofusin 1 [EC:3.6.5.-]
K06030  mitofusin 2 [EC:3.6.5.-]
K07870  mitochondrial Rho GTPase 1 [EC:3.6.5.-]
K07871  mitochondrial Rho GTPase 2 [EC:3.6.5.-]
K02927  ubiquitin-large subunit ribosomal protein L40e
K02977  ubiquitin-small subunit ribosomal protein S27Ae
K04551  ubiquitin B
K08770  ubiquitin C
K21347  Tax1-binding protein 1
K14381  sequestosome 1
K21348  calcium-binding and coiled-coil domain-containing protein 2
K19946  optineurin
K17987  next to BRCA1 gene 1 protein
K05410  TANK-binding kinase 1 [EC:]
K08341  GABA(A) receptor-associated protein
K10435  microtubule-associated protein 1 light chain
K08334  beclin
K11839  ubiquitin carboxyl-terminal hydrolase 8 [EC:]
K21343  ubiquitin carboxyl-terminal hydrolase 15 [EC:]
K11851  ubiquitin carboxyl-terminal hydrolase 30 [EC:]
K04570  Bcl-2-like 1 (apoptosis regulator Bcl-X)
K15637  serine/threonine-protein phosphatase PGAM5 [EC:]
K03097  casein kinase II subunit alpha [EC:]
K03115  casein kinase II subunit beta
K05704  tyrosine-protein kinase Src [EC:]
K21357  serine/threonine-protein kinase ULK1 [EC:]
K17986  FUN14 domain-containing protein 1
K15464  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3
K15465  BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like
K15485  Bcl-2-like protein 13
K09574  FK506-binding protein 8 [EC:]
K07277  outer membrane protein insertion porin family
K17081  prohibitin 2
K12653  NLR family member X1
K17776  metaxin
K08860  eukaryotic translation initiation factor 2-alpha kinase 3 [EC:]
K03237  translation initiation factor 2 subunit 1
K04374  cyclic AMP-dependent transcription factor ATF-4
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:]
K04448  transcription factor AP-1
K04735  transcription factor p65
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K07831  Ras-related protein M-Ras
K07829  Ras-related protein R-Ras
K07830  Ras-related protein R-Ras2
K17454  transcription factor E2F1
K08268  hypoxia-inducible factor 1 alpha
K04684  transcription factor Sp1
K04451  tumor protein p53
K09408  forkhead box protein O3
K21361  Cbp/p300-interacting transactivator 2
K09455  microphthalmia-associated transcription factor
K15590  transcription factor EB
K09105  transcription factor E3
K20131  Rab5 GDP/GTP exchange factor
K07887  Ras-related protein Rab-5A
K07888  Ras-related protein Rab-5B
K07889  Ras-related protein Rab-5C
K20195  vacuolar fusion protein MON1
K27045  vacuolar fusion protein CCZ1, animal type
K07897  Ras-related protein Rab-7A
K07898  Ras-related protein Rab-7B
K20168  TBC1 domain family member 15
K19945  TBC1 domain family member 17
K17969  mitochondrial fission 1 protein
K17907  autophagy-related protein 9
K17079  optic atrophy protein 1 [EC:]
K13525  transitional endoplasmic reticulum ATPase
C00035  GDP
C00044  GTP
Pickrell AM, Youle RJ
The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease.
Neuron 85:257-73 (2015)
Durcan TM, Fon EA
The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications.
Genes Dev 29:989-99 (2015)
Shirihai OS, Song M, Dorn GW 2nd
How mitochondrial dynamism orchestrates mitophagy.
Circ Res 116:1835-49 (2015)
Hamacher-Brady A, Brady NR
Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy.
Cell Mol Life Sci 73:775-95 (2016)
Yamano K, Matsuda N, Tanaka K
The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation.
EMBO Rep 17:300-16 (2016)
Yamaguchi O, Murakawa T, Nishida K, Otsu K
Receptor-mediated mitophagy.
J Mol Cell Cardiol 95:50-6 (2016)
Roberts RF, Tang MY, Fon EA, Durcan TM
Defending the mitochondria: The pathways of mitophagy and mitochondrial-derived vesicles.
Int J Biochem Cell Biol 79:427-436 (2016)
Arena G, Valente EM
PINK1 in the limelight: multiple functions of an eclectic protein in human health and disease.
J Pathol 241:251-263 (2017)
ko04140  Autophagy - animal
ko04210  Apoptosis

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