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McElroy 2020 Cell Metab

From Bioblast
Publications in the MiPMap
McElroy GS, Reczek CR, Reyfman PA, Mithal DS, Horbinski CM, Chandel NS (2020) NAD+ regeneration rescues lifespan, but not ataxia, in a mouse model of brain mitochondrial Complex I dysfunction. Cell Metab 32:301-8.e6. https://doi.org/10.1016/j.cmet.2020.06.003

» PMID: 32574562 Open Access

McElroy GS, Reczek CR, Reyfman PA, Mithal DS, Horbinski CM, Chandel NS (2020) Cell Metab

Abstract: Mitochondrial complex I regenerates NAD+ and proton pumps for TCA cycle function and ATP production, respectively. Mitochondrial complex I dysfunction has been implicated in many brain pathologies including Leigh syndrome and Parkinson's disease. We sought to determine whether NAD+ regeneration or proton pumping, i.e., bioenergetics, is the dominant function of mitochondrial complex I in protection from brain pathology. We generated a mouse that conditionally expresses the yeast NADH dehydrogenase (NDI1), a single enzyme that can replace the NAD+ regeneration capability of the 45-subunit mammalian mitochondrial complex I without proton pumping. NDI1 expression was sufficient to dramatically prolong lifespan without significantly improving motor function in a mouse model of Leigh syndrome driven by the loss of NDUFS4, a subunit of mitochondrial complex I. Therefore, mitochondrial complex I activity in the brain supports organismal survival through its NAD+ regeneration capacity, while optimal motor control requires the bioenergetic function of mitochondrial complex I.

Bioblast editor: Gnaiger E

McElroy 2020 Cell Metab CORRECTION.png

Correction: FADH2 and Complex II

Ambiguity alert.png
FADH2 is shown as the substrate feeding electrons into Complex II (CII). This is wrong and requires correction - for details see Gnaiger (2024).
Gnaiger E (2024) Complex II ambiguities ― FADH2 in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470 - »Bioblast link«