| Literature DB >> 33619377 |
Yuichiro Arima1,2, Yoshiko Nakagawa3, Toru Takeo3, Toshifumi Ishida4, Toshihiro Yamada4, Shinjiro Hino5, Mitsuyoshi Nakao5, Sanshiro Hanada6, Terumasa Umemoto6, Toshio Suda6, Tetsushi Sakuma7, Takashi Yamamoto7, Takehisa Watanabe8, Katsuya Nagaoka8, Yasuhito Tanaka8, Yumiko K Kawamura9,10, Kazuo Tonami9, Hiroki Kurihara9, Yoshifumi Sato11, Kazuya Yamagata11,12, Taishi Nakamura4,13, Satoshi Araki4, Eiichiro Yamamoto4, Yasuhiro Izumiya4,14, Kenji Sakamoto4, Koichi Kaikita4, Kenichi Matsushita4, Koichi Nishiyama6, Naomi Nakagata3, Kenichi Tsujita4,12.
Abstract
Ketone bodies are generated in the liver and allow for the maintenance of systemic caloric and energy homeostasis during fasting and caloric restriction. It has previously been demonstrated that neonatal ketogenesis is activated independently of starvation. However, the role of ketogenesis during the perinatal period remains unclear. Here, we show that neonatal ketogenesis plays a protective role in mitochondrial function. We generated a mouse model of insufficient ketogenesis by disrupting the rate-limiting hydroxymethylglutaryl-CoA synthase 2 enzyme gene (Hmgcs2). Hmgcs2 knockout (KO) neonates develop microvesicular steatosis within a few days of birth. Electron microscopic analysis and metabolite profiling indicate a restricted energy production capacity and accumulation of acetyl-CoA in Hmgcs2 KO mice. Furthermore, acetylome analysis of Hmgcs2 KO cells revealed enhanced acetylation of mitochondrial proteins. These findings suggest that neonatal ketogenesis protects the energy-producing capacity of mitochondria by preventing the hyperacetylation of mitochondrial proteins.Entities:
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Year: 2021 PMID： 33619377 DOI： 10.1038/s42255-021-00342-6
Source DB: PubMed Journal: Nat Metab ISSN： 2522-5812