Oral Presentation 29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019

Endoplasmic reticulum mediates mitochondrial transfer within the osteocyte dendritic network (#39)

Junjie Gao 1 2 3 , An Qin 4 , Delin Liu 1 2 , Rui Ruan 2 , Qiyang Wang 3 , Jun Yuan 1 2 , Tak Sum Cheng 2 , Aleksandra Filipovska 5 , JM Papadimitriou 2 6 , Kerong Dai 4 , Qing Jiang 7 , Xiang Gao 8 , Jian Q. Feng 9 , Hiroshi Takayanagi 2 10 , Changqing Zhang 3 , Ming H. Zheng 1 2
  1. Perron Institute for Neurological and Translational Science , Nedlands, WA, Australia
  2. Centre for Orthopaedic Translational Research, School of Biomedical Sciences, University of Western Australia, Nedlands, WA, Australia
  3. Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China
  4. Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shnaghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicne, Shanghai, China
  5. Centre for Medical Research (affiliated with the Harry Perkins Institute of Medical Research), The University of Western Australia, Nedlands, WA, Australia
  6. Pathwest laboratory, Perth, WA, Australia
  7. Department of Sports Medicine and Adult Reconstruction Surgery, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China
  8. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Collaborative Innovation Center of Genetics and Development, Nanjing University, Nanjing, Jiangsu, China
  9. Biomedical Sciences, Texas A&M Baylor College of Dentistry, Dallas, TX, USA
  10. Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan

Intercellular mitochondrial transfer has attracted a great deal of attention for its major role in the regulation of tissue damage, tissue homeostasis, inflammation and resistance to cancer chemotherapy. Osteocytes are an excellent model to investigate the mechanism of mitochondrial transfer, since osteocytes form an inter-connecting network through their dendritic processes. We demonstrated, in primary murine osteocytes with photo-activatable mitochondria (PhAM)floxed and in MLO-Y4 cells,  mitochondrial transfer in the dendritic networks, visualized by high resolution confocal imaging. Normal, healthy osteocytes transferred mitochondria to adjacent metabolically stressed osteocytes depleted of functional mitochondria and restored their metabolic function. Remarkably, the coordinated movement and transfer of mitochondria within the dendritic network rely on endoplasmic reticulum (ER)-mitochondria contact, predominantly mediated by mitofusin 2 (Mfn2), a GTPase that tethers ER to mitochondria. A decline in Mfn2 expression with age occurs concomitantly with impaired mitochondrial distribution and transfer in the osteocyte dendritic network. These data show a previously unknown function of ER-mitochondrial contact in mediating mitochondrial transfer, and provides a mechanism to explain the complex homeostasis of osteocytes.