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PMID: 22936770 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, U.S. Gov't, Non-P.H.S. Review

Mitochondrial fission, fusion, and stress.

Science (New York, N.Y.) ·Vol. 337 ·No. 6098 ·2012-08-31 ·Pages 1062-5

Youle RJ, van der Bliek AM

Abstract

Mitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses. Fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a form of complementation. Fission is needed to create new mitochondria, but it also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis during high levels of cellular stress. Disruptions in these processes affect normal development, and they have been implicated in neurodegenerative diseases, such as Parkinson's.

MeSH Terms
Animals Autophagy DNA, Mitochondrial/genetics Humans Membrane Fusion Mice Mitochondria/genetics,physiology Mitochondrial Diseases/metabolism Mitochondrial Proteins/genetics,metabolism Mutation Neurodegenerative Diseases/metabolism Parkinson Disease/metabolism Stress, Physiological
Chemicals
DNA, Mitochondrial Mitochondrial Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Youle Richard J
Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. youler@ninds.nih.gov
van der Bliek Alexander M
References (44)
44 references, click to expand
  1. Analysis of neural subtypes reveals selective mitochondrial dysfunction in dopaminergic neurons from parkin mutants.
    Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10438-43 PMID: 22691499
  2. A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations.
    Science. 2008 Feb 15;319(5865):958-62 PMID: 18276892
  3. Emerging role for members of the Bcl-2 family in mitochondrial morphogenesis.
    Mol Cell. 2009 Nov 13;36(3):355-63 PMID: 19917245
  4. SLP-2 is required for stress-induced mitochondrial hyperfusion.
    EMBO J. 2009 Jun 3;28(11):1589-600 PMID: 19360003
  5. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy.
    Science. 2011 Jan 28;331(6016):456-61 PMID: 21205641
  6. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy.
    J Cell Biol. 2008 Dec 1;183(5):795-803 PMID: 19029340
  7. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin.
    Nature. 2006 Jun 29;441(7097):1157-61 PMID: 16672980
  8. Mitophagy selectively degrades individual damaged mitochondria after photoirradiation.
    Antioxid Redox Signal. 2011 May 15;14(10):1919-28 PMID: 21126216
  9. Quality control of mitochondrial proteostasis.
    Cold Spring Harb Perspect Biol. 2011 Jul 01;3(7): PMID: 21628427
  10. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin.
    J Cell Biol. 2010 Dec 27;191(7):1367-80 PMID: 21173115
  11. Functional F1-ATPase essential in maintaining growth and membrane potential of human mitochondrial DNA-depleted rho degrees cells.
    J Biol Chem. 1998 Sep 4;273(36):22983-9 PMID: 9722521
  12. Complementation of mutant and wild-type human mitochondrial DNAs coexisting since the mutation event and lack of complementation of DNAs introduced separately into a cell within distinct organelles.
    Mol Cell Biol. 1994 Apr;14(4):2699-712 PMID: 8139569
  13. Disruption of fusion results in mitochondrial heterogeneity and dysfunction.
    J Biol Chem. 2005 Jul 15;280(28):26185-92 PMID: 15899901
  14. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice.
    J Cell Biol. 2005 May 9;169(3):425-34 PMID: 15866887
  15. Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation.
    Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10190-5 PMID: 21646527
  16. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy.
    EMBO J. 2008 Jan 23;27(2):433-46 PMID: 18200046
  17. Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells.
    J Cell Biol. 2009 Dec 28;187(7):959-66 PMID: 20038677
  18. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility.
    Cell. 2011 Nov 11;147(4):893-906 PMID: 22078885
  19. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability.
    Nat Cell Biol. 2011 May;13(5):589-98 PMID: 21478857
  20. Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1.
    Cell. 2006 Oct 20;127(2):383-95 PMID: 17055438
  21. Asymmetric segregation of protein aggregates is associated with cellular aging and rejuvenation.
    Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3076-81 PMID: 18287048
  22. Functional complementation of mitochondrial DNAs: mobilizing mitochondrial genetics against dysfunction.
    Biochim Biophys Acta. 2010 Mar;1800(3):245-9 PMID: 19616602
  23. The evolution and role of mitochondrial fusion and fission in aging and disease.
    Commun Integr Biol. 2011 Sep;4(5):627-9 PMID: 22046482
  24. Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization.
    Cell. 2010 Sep 17;142(6):889-901 PMID: 20850011
  25. Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells.
    Cancer Res. 2004 Feb 1;64(3):985-93 PMID: 14871829
  26. Physiological functions of mitochondrial fusion.
    Ann N Y Acad Sci. 2010 Jul;1201:21-5 PMID: 20649534
  27. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin.
    Nature. 2006 Jun 29;441(7097):1162-6 PMID: 16672981
  28. Asymmetric mitosis: Unequal segregation of proteins destined for degradation.
    Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7732-7 PMID: 18511557
  29. Strong purifying selection in transmission of mammalian mitochondrial DNA.
    PLoS Biol. 2008 Jan;6(1):e10 PMID: 18232733
  30. Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.
    Nucleic Acids Res. 2012 Jul;40(13):6109-21 PMID: 22453275
  31. Mitochondrial dynamics and apoptosis.
    Genes Dev. 2008 Jun 15;22(12):1577-90 PMID: 18559474
  32. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
    Nature. 1998 Apr 9;392(6676):605-8 PMID: 9560156
  33. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4078-83 PMID: 12642658
  34. Inter-mitochondrial complementation: Mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA.
    Nat Med. 2001 Aug;7(8):934-40 PMID: 11479626
  35. Hereditary early-onset Parkinson's disease caused by mutations in PINK1.
    Science. 2004 May 21;304(5674):1158-60 PMID: 15087508
  36. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes.
    Curr Biol. 2012 Jan 24;22(2):135-41 PMID: 22226745
  37. Mitochondria, oxidants, and aging.
    Cell. 2005 Feb 25;120(4):483-95 PMID: 15734681
  38. The machines that divide and fuse mitochondria.
    Annu Rev Biochem. 2007;76:751-80 PMID: 17362197
  39. Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.
    Science. 2012 Aug 3;337(6094):587-90 PMID: 22700657
  40. ER tubules mark sites of mitochondrial division.
    Science. 2011 Oct 21;334(6054):358-62 PMID: 21885730
  41. Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration.
    Nat Med. 2010 Nov;16(11):1313-20 PMID: 21037586
  42. Selective autophagy mediated by autophagic adapter proteins.
    Autophagy. 2011 Mar;7(3):279-96 PMID: 21189453
  43. Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster.
    Cell Death Differ. 2012 Aug;19(8):1308-16 PMID: 22301916
  44. Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1.
    J Cell Biol. 2009 Dec 28;187(7):1023-36 PMID: 20038678
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1219855
Email
youler@ninds.nih.gov
Published
2012-08-31
Pages
1062-5
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC4762028
Subset
IM
Grants
NIGMS NIH HHS · R01 GM051866 · United States
Intramural NIH HHS · Z99 NS999999 · United States
NIGMS NIH HHS · GM051866 · United States
Corrections
CommentIn
PMID: 22936767
External Links
PubMed source DOI: 10.1126/science.1219855 PMC Full Text View journal details
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