Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development.
Cell proliferation and tissue growth depend on the coordinated regulation of multiple signaling molecules and pathways during animal development. Previous studies have linked mitochondrial function and the Hippo signaling pathway in growth control. However, the underlying molecular mechanisms are not fully understood. Here we identify a Drosophila mitochondrial inner membrane protein ChChd3 as a novel regulator for tissue growth. Loss of ChChd3 leads to tissue undergrowth and cell proliferation defects. ChChd3 is required for mitochondrial fusion and removal of ChChd3 increases mitochondrial fragmentation. ChChd3 is another mitochondrial target of the Hippo pathway, although it is only partially required for Hippo pathway-mediated overgrowth. Interestingly, lack of ChChd3 leads to inactivation of Hippo activity under normal development, which is also dependent on the transcriptional coactivator Yorkie (Yki). Furthermore, loss of ChChd3 induces oxidative stress and activates the JNK pathway. In addition, depletion of other mitochondrial fusion components, Opa1 or Marf, inactivates the Hippo pathway as well. Taken together, we propose that there is a cross-talk between mitochondrial fusion and the Hippo pathway, which is essential in controlling cell proliferation and tissue homeostasis in Drosophila.
Division of Human Reproduction and Developmental Genetics, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China 310058 Institute of Genetics and College of Life Sciences, Zhejiang University, Hangzhou, China 310058, Zhejiang University, and.
Qiannan
Q
Deng
Division of Human Reproduction and Developmental Genetics, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China 310058 Institute of Genetics and College of Life Sciences, Zhejiang University, Hangzhou, China 310058, Zhejiang University, and.
Ting
T
Guo
College of Life Sciences, Zhejiang University, Hangzhou, China 310058, Zhejiang University, and.
Xiu
X
Zhou
Division of Human Reproduction and Developmental Genetics, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China 310058 Institute of Genetics and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, China 310058.
Yongmei
Y
Xi
Division of Human Reproduction and Developmental Genetics, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China 310058 Department of Genetics, Zhejiang University School of Medicine, Hangzhou, China 310058 Institute of Genetics and xhyang@zju.edu.cn wanzhongge@zju.edu.cn.
Xiaohang
X
Yang
Division of Human Reproduction and Developmental Genetics, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China 310058 Institute of Genetics and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, China 310058 xhyang@zju.edu.cn wanzhongge@zju.edu.cn.
Wanzhong
W
Ge
D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D063154:Mitochondrial Dynamics / Q000235:genetics; D051336:Mitochondrial Membranes / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C000619233:ChChd3 protein, Drosophila; C527117:Marf protein, Drosophila; C527116:OPA1 protein, Drosophila; C503814:Yki protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
ChChd3; Hippo pathway; cell proliferation; mitochondria