Inflexibility of AMPK-mediated metabolic reprogramming in mitochondrial disease

Oncotarget
Dar-Shong LinMing-Fu Chiang

Abstract

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is most commonly caused by the A3243G mutation of mitochondrial DNA. The capacity to utilize fatty acid or glucose as a fuel source and how such dynamic switches of metabolic fuel preferences and transcriptional modulation of adaptive mechanism in response to energy deficiency in MELAS syndrome have not been fully elucidated. The fibroblasts from patients with MELAS syndrome demonstrated a remarkable deficiency of electron transport chain complexes I and IV, an impaired cellular biogenesis under glucose deprivation, and a decreased ATP synthesis. In situ analysis of the bioenergetic properties of MELAS cells demonstrated an attenuated fatty acid oxidation that concomitantly occurred with impaired mitochondrial respiration, while energy production was mostly dependent on glycolysis. Furthermore, the transcriptional modulation was mediated by the AMP-activated protein kinase (AMPK) signaling pathway, which activated its downstream modulators leading to a subsequent increase in glycolytic flux through activation of pyruvate dehydrogenase. In contrast, the activities of carnitine palmitoyltransferase for fatty acid oxidation and acetyl-CoA c...Continue Reading

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Citations

Jan 21, 2021·Biochemical and Biophysical Research Communications·Taichi FukunagaKazuhiro Shigemoto
Mar 26, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Andrea Pozzi, Damian K Dowling
Feb 18, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Marina Villanueva-PazJosé A Sánchez-Alcázar

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Methods Mentioned

BETA
biopsies
acetylation
Assay
electrophoresis

Software Mentioned

Primer3

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