Mitochondria are critical for proper organ function and mechanisms to promote mitochondrial health during regeneration would benefit tissue homeostasis. We report that during liver regeneration, proliferation is suppressed in electron transport chain (ETC)–dysfunctional hepatocytes due to an inability to generate acetyl-CoA from peripheral fatty acids through mitochondrial β-oxidation. Alternative modes for acetyl-CoA production from pyruvate or acetate are suppressed in the setting of ETC dysfunction. This metabolic inflexibility forces a dependence on ETC-functional mitochondria and restoring acetyl-CoA production from pyruvate is sufficient to allow ETC-dysfunctional hepatocytes to proliferate. We propose that metabolic inflexibility within hepatocytes can be advantageous by limiting the expansion of ETC-dysfunctional cells.

中文翻译：

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代谢不灵活促进肝脏再生过程中的线粒体健康


线粒体对于器官的正常功能至关重要，在再生过程中促进线粒体健康的机制将有利于组织稳态。我们报告说，在肝脏再生过程中，电子传递链（ETC）功能失调的肝细胞的增殖受到抑制，因为无法通过线粒体β-氧化从外周脂肪酸产生乙酰辅酶A。在 ETC 功能障碍的情况下，从丙酮酸或乙酸盐生成乙酰辅酶 A 的替代模式受到抑制。这种代谢不灵活迫使对 ETC 功能线粒体的依赖，并且恢复丙酮酸乙酰辅酶 A 的产生足以使 ETC 功能障碍的肝细胞增殖。我们认为，肝细胞内代谢的不灵活性可以通过限制 ETC 功能障碍细胞的扩张而发挥优势。