KEGG   PATHWAY: cel04137
Entry
cel04137                    Pathway                                
Name
Mitophagy - animal - Caenorhabditis elegans (nematode)
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 catabolism
Pathway map
cel04137  Mitophagy - animal
cel04137

Other DBs
GO: 0000422
Organism
Caenorhabditis elegans (nematode) [GN:cel]
Gene
CELE_EEED8.9  pink-1; Serine/threonine-protein kinase pink-1, mitochondrial [KO:K05688] [EC:2.7.11.1]
CELE_ZK652.2  tomm-7; Mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
CELE_C18E9.6  tomm-40; Mitochondrial import receptor subunit TOM40 homolog [KO:K11518]
CELE_F23H12.2  tomm-20; Mitochondrial import receptor subunit TOM20 homolog [KO:K17770]
CELE_K08E3.7  pdr-1; E3 ubiquitin-protein ligase parkin [KO:K04556] [EC:2.3.2.31]
CELE_F26E4.11  hrdl-1; E3 ubiquitin-protein ligase hrd-like protein 1 [KO:K10636] [EC:2.3.2.36]
CELE_Y67D8C.5  eel-1; HECT-type E3 ubiquitin transferase [KO:K10592] [EC:2.3.2.26]
CELE_Y37E11AR.2  siah-1; E3 ubiquitin-protein ligase siah-1 [KO:K04506] [EC:2.3.2.27]
CELE_C27A12.8  ari-1.1; E3 ubiquitin-protein ligase ari-1.1 [KO:K11968] [EC:2.3.2.31]
CELE_ZK1248.14  fzo-1; Transmembrane GTPase fzo-1 [KO:K06030] [EC:3.6.5.-]
CELE_K08F11.5  miro-1; Mitochondrial Rho GTPase 1 [KO:K07870] [EC:3.6.5.-]
CELE_ZK1010.1  ubq-2; Ubiquitin [KO:K02927]
CELE_F34H10.1  F34H10.1; putative ribosomal protein F34H10.1 [KO:K02977]
CELE_H06I04.4  ubl-1; Ubiquitin-like protein 1 [KO:K02977]
CELE_F25B5.4  ubq-1; Ubiquitin-related [KO:K08770]
CELE_C32D5.9  lgg-1; Protein lgg-1 [KO:K08341]
CELE_ZK593.6  lgg-2; Protein lgg-2 [KO:K10435]
CELE_T19E7.3  bec-1; Beclin homolog [KO:K08334]
CELE_E01B7.1  usp-50; USP domain-containing protein [KO:K11839] [EC:3.4.19.12]
CELE_Y67D2.2  Y67D2.2; Ubiquitin carboxyl-terminal hydrolase [KO:K11851] [EC:3.4.19.12]
CELE_R07G3.5  pgam-5; Serine/threonine-protein phosphatase Pgam5, mitochondrial [KO:K15637] [EC:3.1.3.16]
CELE_B0205.7  kin-3; Casein kinase II subunit alpha [KO:K03097] [EC:2.7.11.1]
CELE_T01G9.6  kin-10; Casein kinase II subunit beta [KO:K03115]
CELE_Y92H12A.1  src-1; Tyrosine protein-kinase src-1 [KO:K05704] [EC:2.7.10.2]
CELE_T06D8.7  fndc-1; FUN14 domain-containing protein fndc-1 [KO:K17986]
CELE_C14F5.1  dct-1; NIP3 homolog [KO:K15464]
CELE_C34E10.1  gop-3; SAM50-like protein gop-3 [KO:K07277]
CELE_T24H7.1  phb-2; Mitochondrial prohibitin complex protein 2 [KO:K17081]
CELE_F39B2.11  mtx-1; Metaxin-1 homolog [KO:K17776]
CELE_ZC97.1  mtx-2; Metaxin-2 homolog [KO:K17776]
CELE_F46C3.1  pek-1; Eukaryotic translation initiation factor 2-alpha kinase pek-1 [KO:K08860] [EC:2.7.11.1]
CELE_Y37E3.10  eif-2alpha; Eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
CELE_T04C10.4  atf-4; Transcription factor atf-4 homolog [KO:K04374]
CELE_B0478.1  jnk-1; Stress-activated protein kinase jnk-1 [KO:K04440] [EC:2.7.11.24]
CELE_T07A9.3  kgb-1; GLH-binding kinase 1 [KO:K04440] [EC:2.7.11.24]
CELE_ZC416.4  kgb-2; Stress-activated protein kinase JNK [KO:K04440] [EC:2.7.11.24]
CELE_ZK792.6  let-60; Ras protein let-60 [KO:K07827]
CELE_F17C8.4  ras-2; R-RAS related [KO:K07831]
CELE_C44C11.1  ras-1; R-RAS related [KO:K07830]
CELE_F38A6.3  hif-1; Hypoxia-inducible factor 1 [KO:K08268]
CELE_R13H8.1  daf-16; Forkhead box protein O [KO:K09408]
CELE_Y39A1A.5  rabx-5; Rab5 GDP/GTP exchange factor [KO:K20131]
CELE_F26H9.6  rab-5; Ras-related protein Rab-5C [KO:K07888]
CELE_F41H10.11  sand-1; Vacuolar fusion protein MON1 homolog [KO:K20195]
CELE_F58G11.6  ccz-1; Vacuolar fusion protein CCZ1 homolog [KO:K27045]
CELE_W03C9.3  rab-7; Ras-related protein Rab-7a [KO:K07897]
CELE_E01G4.1  tbc-14; Rab-GAP TBC domain-containing protein [KO:K20168]
CELE_F13B9.8  fis-2; FIS1-related protein fis-2 [KO:K17969]
CELE_T22H9.2  atg-9; Autophagy-related protein 9 [KO:K17907]
CELE_D2013.5  eat-3; Dynamin-like 120 kDa protein, mitochondrial [KO:K17079] [EC:3.6.5.5]
CELE_C41C4.8  cdc-48.2; Transitional endoplasmic reticulum ATPase homolog 2 [KO:K13525]
CELE_C06A1.1  cdc-48.1; Transitional endoplasmic reticulum ATPase homolog 1 [KO:K13525]
Compound
C00035  GDP
C00044  GTP
Reference
  Authors
Pickrell AM, Youle RJ
  Title
The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease.
  Journal
Neuron 85:257-73 (2015)
DOI:10.1016/j.neuron.2014.12.007
Reference
  Authors
Durcan TM, Fon EA
  Title
The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications.
  Journal
Genes Dev 29:989-99 (2015)
DOI:10.1101/gad.262758.115
Reference
  Authors
Shirihai OS, Song M, Dorn GW 2nd
  Title
How mitochondrial dynamism orchestrates mitophagy.
  Journal
Circ Res 116:1835-49 (2015)
DOI:10.1161/CIRCRESAHA.116.306374
Reference
  Authors
Hamacher-Brady A, Brady NR
  Title
Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy.
  Journal
Cell Mol Life Sci 73:775-95 (2016)
DOI:10.1007/s00018-015-2087-8
Reference
  Authors
Yamano K, Matsuda N, Tanaka K
  Title
The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation.
  Journal
EMBO Rep 17:300-16 (2016)
DOI:10.15252/embr.201541486
Reference
  Authors
Yamaguchi O, Murakawa T, Nishida K, Otsu K
  Title
Receptor-mediated mitophagy.
  Journal
J Mol Cell Cardiol 95:50-6 (2016)
DOI:10.1016/j.yjmcc.2016.03.010
Reference
  Authors
Roberts RF, Tang MY, Fon EA, Durcan TM
  Title
Defending the mitochondria: The pathways of mitophagy and mitochondrial-derived vesicles.
  Journal
Int J Biochem Cell Biol 79:427-436 (2016)
DOI:10.1016/j.biocel.2016.07.020
Reference
  Authors
Arena G, Valente EM
  Title
PINK1 in the limelight: multiple functions of an eclectic protein in human health and disease.
  Journal
J Pathol 241:251-263 (2017)
DOI:10.1002/path.4815
Related
pathway
cel04140  Autophagy - animal
KO pathway
ko04137   
LinkDB

DBGET integrated database retrieval system