Mitochondrial Membrane Potential Heterogeneity in Cancer Cells is Independent of the Cell Cycle and Influences Response to Hyperpolarizing Agents

Abstract

arachidic) consistent with the changes observed in liver's metabolome. Higher liver AMP levels in HCR vs. LCR suggest activation of AMPK signaling, in agreement with the enhanced autophagy/mitophagy observed in HCR. Importantly, the higher relative LCR/HCR fold-changes of acetylated intermediates, in both liver and serum, agrees with the idea of widespread increased acetylation, compatible with the higher concentration of AcCoA measured in cardiomyocytes from LCR vs. HCR. Metabolomics reveal systemic, organ-concerted (liver-serum-heart), metabolic remodeling compatible with higher energetic performance, better preserved mitochondrial turnover, preferential lipid oxidation, and improved control of acetylation in HCR leading to extended longevity and better functional capacity.