α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line.
Life (Basel)
; 12(6)2022 Jun 15.
Article
in En
| MEDLINE
| ID: mdl-35743925
ABSTRACT
α-synuclein (αSyn) is a small neuronal protein whose accumulation correlates with Parkinson's disease. αSyn A53T mutant impairs mitochondrial functions by affecting substrate import within the organelle, activity of complex I and the maximal respiratory capacity. However, the precise mechanism initiating the bioenergetic dysfunction is not clearly understood yet. By overexpressing αSyn A53T in SH-SY5Y cells, we investigated the specific changes in the mitochondrial respiratory profile using High-Resolution Respirometry. We found that αSyn A53T increases dissipative fluxes across the intermembrane mitochondrial space this does not compromise the oxygen flows devoted to ATP production while it reduces the bioenergetic excess capacity of mitochondria, providing a possible explanation of the increased cell susceptibility observed in the presence of further stress stimuli.
Full text:
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Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Life (Basel)
Year:
2022
Document type:
Article
Affiliation country:
Italy