机构：[1]Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine and Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.[2]Electron Microscopy Facility, Case Western Reserve University, Cleveland, Ohio, USA.[3]Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.[4]Department of Cardiology, Beijing Anzhen Hospital, Beijing Capital Medical University, Beijing, China.临床科室心脏内科中心首都医科大学附属安贞医院[5]Illinois Mathematics and Science Academy, Aurora, IL, USA.[6]Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
Brown adipose tissue (BAT) is a specialized thermogenic organ in mammals. The ability of BAT mitochondria to generate heat in response to cold-challenge to maintain core body temperature is essential for organismal survival. While cold activated BAT mitochondrial biogenesis is recognized as critical for thermogenic adaptation, the contribution of mitochondrial quality control to this process remains unclear. Here, we show mitophagy is required for brown adipocyte mitochondrial homeostasis during thermogenic adaptation. Mitophagy is significantly increased in BAT from cold-challenged mice (4 degrees C) and in beta-agonist treated brown adipocytes. Blockade of mitophagy compromises brown adipocytes mitochondrial oxidative phosphorylation (OX-PHOS) capacity, as well as BAT mitochondrial integrity. Mechanistically, cold-challenge induction of BAT mitophagy is UCP1-dependent. Furthermore, our results indicate that mitophagy coordinates with mitochondrial biogenesis, maintaining activated BAT mitochondrial homeostasis. Collectively, our in vivo and in vitro findings identify mitophagy as critical for brown adipocyte mitochondrial homeostasis during cold adaptation.
基金：
American Heart Association National Scientist Development grant AHA SDG grant [12050558]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01HL119195, R01HL086548, R01HL123098]
第一作者机构：[1]Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine and Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
通讯作者：
通讯机构：[1]Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine and Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
推荐引用方式(GB/T 7714)：
Yuan Lu,Hisashi Fujioka,Dinesh Joshi,et al.Mitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge[J].SCIENTIFIC REPORTS.2018,8(1):-.doi:10.1038/s41598-018-26394-5.
APA：
Yuan Lu,Hisashi Fujioka,Dinesh Joshi,Qiaoyuan Li,Panjamaporn Sangwung...&Mukesh K. Jain.(2018).Mitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge.SCIENTIFIC REPORTS,8,(1)
MLA：
Yuan Lu,et al."Mitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge".SCIENTIFIC REPORTS 8..1(2018):-
