Abstract
Mitochondrial function is central to longevity and an imbalance in mitonuclear protein homeostasis activates a protective response called the mitochondrial unfolded protein response (UPRmt). Toxic compounds damaging mitochondria trigger the UPRmt, but at sublethal doses these insults extend lifespan in simple animals like C. elegans. Mitochondria are the main energy suppliers in eukaryotes, but it is not known if diet influences the UPRmt. High dietary glucose reduces lifespan in worms, and we show that high dietary glucose activates the UPRmt to protect against lifespan reduction. While lifelong exposure to glucose reduces lifespan, glucose exposure restricted to developing animals extends lifespan and requires the UPRmt. However, this lifespan extension is abolished by further mitochondrial stress in adult animals. We demonstrate that dietary conditions regulate mitochondrial homeostasis, where induction of the UPRmt during development extends lifespan, but prolonged activation into adulthood reduces lifespan.
References
Nov 16, 2001·Developmental Cell·J FengS Hekimi
Feb 7, 2002·Biochemical and Biophysical Research Communications·William Y Tsang, Bernard D Lemire
Jul 4, 2006·Genetics·Cristina BenedettiDavid Ron
Oct 3, 2007·Cell Metabolism·Tim J SchulzMichael Ristow
Oct 5, 2007·PLoS Biology·Shane L ReaThomas E Johnson
Oct 11, 2007·Developmental Cell·Cole M HaynesDavid Ron
Feb 7, 2009·PLoS Genetics·Jeremy M Van Raamsdonk, Siegfried Hekimi
Nov 4, 2009·Cell Metabolism·Seung-Jae LeeCynthia Kenyon
Dec 15, 2010·PLoS Biology·Wen Yang, Siegfried Hekimi
Jan 11, 2011·Cell·Jenni DurieuxAndrew Dillin
Jun 16, 2012·Science·Amrita M NargundCole M Haynes
Jun 28, 2012·Aging Cell·Arnaud TauffenbergerJ Alex Parker
Aug 9, 2012·Antioxidants & Redox Signaling·David Gems, Yila de la Guardia
May 24, 2013·Nature·Riekelt H HoutkooperJohan Auwerx
Feb 25, 2014·Cell Metabolism·Jeanho Yun, Toren Finkel
Apr 4, 2014·Nature·Ying LiuGary Ruvkun
Jul 8, 2014·Nature Medicine·Michael Ristow
Feb 26, 2015·Diabetes·Kumar Sharma
Feb 28, 2015·Cell·Kristopher BurkewitzWilliam B Mair
May 11, 2015·Cell·Dirk M WaltherF Ulrich Hartl
Citations
Dec 13, 2016·Cellular and Molecular Life Sciences : CMLS·Dongyeop LeeSeung-Jae V Lee
Mar 30, 2018·Molecular Neurobiology·Gerwyn MorrisAndré F Carvalho
Jan 31, 2020·Human Genetics·Joseph C ReynoldsChanghan Lee
Sep 12, 2019·Cell Death & Disease·Arnaud TauffenbergerPierre J Magistretti
May 1, 2021·Antioxidants·Patrick C Bradshaw
Apr 2, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shanmugam GovindanSundararaj Palanisamy