TRABD modulates mitochondrial homeostasis and tissue integrity
Caixia Zhou,
Zhirong Li,
Yawen Li,
Yaoyao Li,
Wei Wang,
Weina Shang,
Jun-Ping Liu,
Liquan Wang,
Chao Tong
Affiliations
Caixia Zhou
MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China
Zhirong Li
MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China
Yawen Li
MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China
Yaoyao Li
MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
Wei Wang
MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China
Weina Shang
MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
Jun-Ping Liu
Institute of Aging Research, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
Liquan Wang
Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China
Chao Tong
MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China; Institute of Aging Research, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen 518132, China; Corresponding author
Summary: High TRABD expression is associated with tau pathology in patients with Alzheimer’s disease; however, the function of TRABD is unknown. Human TRABD encodes a mitochondrial outer-membrane protein. The loss of TRABD resulted in mitochondrial fragmentation, and TRABD overexpression led to mitochondrial clustering and fusion. The C-terminal tail of the TRABD anchored to the mitochondrial outer membrane and the TraB domain could form homocomplexes. Additionally, TRABD forms complexes with MFN2, MIGA2, and PLD6 to facilitate mitochondrial fusion. Flies lacking dTRABD are viable and have normal lifespans. However, aging flies exhibit reduced climbing ability and abnormal mitochondrial morphology in their muscles. The expression of dTRABD is increased in aged flies. dTRABD overexpression leads to neurodegeneration and enhances tau toxicity in fly eyes. The overexpression of dTRABD also increased reactive oxygen species (ROS), ATP production, and protein turnover in the mitochondria. This study suggested that TRABD-induced mitochondrial malfunctions contribute to age-related neurodegeneration.
