PMID- 30601141
OWN - NLM
STAT- MEDLINE
DCOM- 20191105
LR  - 20200309
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 129
IP  - 1
DP  - 2019 Jan 2
TI  - Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of 
      gas.
PG  - 34-45
LID - 120848 [pii]
LID - 10.1172/JCI120848 [doi]
AB  - Mitochondrial respiratory deficiencies have been observed in numerous 
      neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. For 
      decades, these reductions in oxidative phosphorylation (OxPhos) have been 
      presumed to trigger an overall bioenergetic crisis in the neuron, resulting in 
      cell death. While the connection between respiratory defects and neuronal death 
      has never been proven, this hypothesis has been supported by the detection of 
      nonspecific mitochondrial DNA mutations in these disorders. These findings led to 
      the notion that mitochondrial respiratory defects could be initiators of these 
      common neurodegenerative disorders, instead of being consequences of a prior 
      insult, a theory we believe to be misconstrued. Herein, we review the roots of 
      this mitochondrial hypothesis and offer a new perspective wherein mitochondria 
      are analyzed not only from the OxPhos point of view, but also as a complex 
      organelle residing at the epicenter of many metabolic pathways.
FAU - Area-Gomez, Estela
AU  - Area-Gomez E
AD  - Department of Neurology.
FAU - Guardia-Laguarta, Cristina
AU  - Guardia-Laguarta C
AD  - Department of Pathology and Cell Biology, and.
FAU - Schon, Eric A
AU  - Schon EA
AD  - Department of Neurology.
AD  - Department of Genetics and Development, Columbia University Medical Center, New 
      York, New York, USA.
FAU - Przedborski, Serge
AU  - Przedborski S
AD  - Department of Pathology and Cell Biology, and.
LA  - eng
GR  - R01 AG056387/AG/NIA NIH HHS/United States
GR  - R01 NS107442/NS/NINDS NIH HHS/United States
GR  - R01 EB009041/EB/NIBIB NIH HHS/United States
GR  - R21 NS099862/NS/NINDS NIH HHS/United States
GR  - K01 AG045335/AG/NIA NIH HHS/United States
GR  - P01 HD032062/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
DEP - 20190102
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (DNA, Mitochondrial)
SB  - IM
MH  - Alzheimer Disease/genetics/*metabolism/pathology
MH  - Animals
MH  - Cell Death
MH  - DNA, Mitochondrial/genetics/metabolism
MH  - Humans
MH  - Mitochondria/genetics/*metabolism/pathology
MH  - *Models, Neurological
MH  - Mutation
MH  - Neurons/*metabolism/pathology
MH  - *Oxidative Phosphorylation
MH  - Parkinson Disease/genetics/*metabolism/pathology
PMC - PMC6307938
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2019/01/03 06:00
MHDA- 2019/11/07 06:00
PMCR- 2020/01/02
CRDT- 2019/01/03 06:00
PHST- 2019/01/03 06:00 [entrez]
PHST- 2019/01/03 06:00 [pubmed]
PHST- 2019/11/07 06:00 [medline]
PHST- 2020/01/02 00:00 [pmc-release]
AID - 120848 [pii]
AID - 10.1172/JCI120848 [doi]
PST - ppublish
SO  - J Clin Invest. 2019 Jan 2;129(1):34-45. doi: 10.1172/JCI120848. Epub 2019 Jan 2.