Kakimoto 2021 Redox Biol

From Bioblast
Publications in the MiPMap
Kakimoto PA, Serna JDC, de Miranda Ramos V, Zorzano A, Kowaltowski AJ (2021) Increased glycolysis is an early consequence of palmitate lipotoxicity mediated by redox signaling. Redox Biol 45:102026.

Β» PMID: 34102573 Open Access

Kakimoto Pamela A, Serna Julian David C, de Miranda Ramos Vitor, Zorzano Antonio, Kowaltowski Alicia J (2021) Redox Biol

Abstract: Exposure to toxic levels of fatty acids (lipotoxicity) leads to cell damage and death and is involved in the pathogenesis of the metabolic syndrome. Since the metabolic consequences of lipotoxicity are still poorly understood, we studied the bioenergetic effects of the saturated fatty acid palmitate, quantifying changes in mitochondrial morphology, real-time oxygen consumption, ATP production sources, and extracellular acidification in hepatoma cells. Surprisingly, glycolysis was enhanced by the presence of palmitate as soon as 1 h after stimulus, while oxygen consumption and oxidative phosphorylation were unchanged, despite overt mitochondrial fragmentation. Palmitate only induced mitochondrial fragmentation if glucose and glutamine were available, while glycolytic enhancement did not require glutamine, showing it is independent of mitochondrial morphological changes. Redox state was altered by palmitate, as indicated by NAD(P)H quantification. Furthermore, the mitochondrial antioxidant mitoquinone, or a selective inhibitor of complex I electron leakage (S1QEL) further enhanced palmitate-induced glycolysis. Our results demonstrate that palmitate overload and lipotoxicity involves an unexpected and early increase in glycolytic flux, while, surprisingly, no changes in oxidative phosphorylation are observed. Interestingly, enhanced glycolysis involves signaling by mitochondrially-generated oxidants, uncovering a novel regulatory mechanism for this pathway. β€’ Keywords: Glycolysis, Mitochondria, Oxidative stress, Palmitic acid, Reactive oxygen species β€’ Bioblast editor: Reiswig R β€’ O2k-Network Lab: ES Barcelona Zorzano A, BR Sao Paulo Kowaltowski AJ

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Human  Tissue;cell: Liver  Preparation: Permeabilized cells 

Regulation: Fatty acid  Coupling state: LEAK, OXPHOS  Pathway: N, S, NS  HRR: Oxygraph-2k 


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