The energetics of cellular life transitions  

作　　者：Anna S.Monzel Michael Levin Martin Picard 

机构地区：[1]Department of Psychiatry,Division of Behavioral Medicine,College of Physicians and Surgeons,Columbia University Irving Medical Center,New York,NY 10032,United States [2]Department of Biology,Tufts University,Medford,MA 02155,United States [3]Allen Discovery Center at Tufts University,Medford,MA 02155,United States [4]Wyss Institute for Biologically Inspired Engineering,Harvard University,Boston,MA 02115,United States [5]Department of Neurology,H.Houston Merritt Center,Columbia Translational Neuroscience Initiative,College of Physicians and Surgeons,Columbia University Irving Medical Center,New York,NY 10032,United States [6]New York State Psychiatric Institute,New York,NY 10032,United States [7]Robert N Butler Columbia Aging Center,Columbia University Mailman School of Public Health,New York,NY 10032,United States

出　　处：《Life Metabolism》2024年第3期12-20,共9页生命代谢（英文）

基　　金：supported by grants from the NIH(R01MH119336,R01MH122706,R01AG066828,and RF1AG076821);the Wharton Fund,and the Baszucki Brain Research Fund to M.P.M.L.gratefully acknowledges support from the Templeton World Charity Foundation(TWCF0606);the Bill and Melinda Gates Foundation.

摘　　要：Major life transitions are always difficult because change costs energy.Recent findings have demonstrated how mitochondrial oxidative phosphorylation(OxPhos)defects increase the energetic cost of living and that excessive integrated stress response(ISR)signaling may prevent cellular identity transitions during development.In this perspective,we discuss general bioenergetic principles of life transitions and the costly molecular processes involved in reprograming the cellular hardware/software as cells shift identity.The energetic cost of cellular differentiation has not been directly quantified,representing a gap in knowledge.We propose that the ISR is an energetic checkpoint evolved to(i)prevent OxPhos-deficient cells from engaging in excessively costly transitions and(ii)allow ISR-positive cells to recruit systemic energetic resources by signaling via GDF15 and the brain.

关 键 词：ENERGY MITOCHONDRIA signaling pathway growth differentiation factor 15 energy balance DEVELOPMENT 

分 类 号：Q251[生物学—细胞生物学]