Saurabh Mishra, Nicole Welch, Manikandan Karthikeyan, Annette Bellar, Ryan Musich, Shashi Shekhar Singh, Dongmei Zhang, Jinendiran Sekar, Amy H Attaway, Aruna Kumar Chelluboyina, Shuhui Wang Lorkowski, Sanjoy Roychowdhury, Ling Li, Belinda Willard, Jonathan D Smith, Charles L Hoppel, Vidula Vachharajani, Avinash Kumar, Srinivasan Dasarathy
Perturbed metabolism of ammonia, an endogenous cytotoxin, causes mitochondrial dysfunction, reduced NAD+ /NADH (redox) ratio, and postmitotic senescence. Sirtuins are NAD+ -dependent deacetylases that delay senescence. In multiomics analyses, NAD metabolism and sirtuin pathways are enriched during hyperammonemia. Consistently, NAD+ -dependent Sirtuin3 (Sirt3) expression and deacetylase activity were decreased, and protein acetylation was increased in human and murine skeletal muscle/myotubes. Global acetylomics and subcellular fractions from myotubes showed hyperammonemia-induced hyperacetylation of cellular signaling and mitochondrial proteins...
July 2023: Aging Cell