title: Transfer of mitochondria from astrocytes to neurons after stroke.
abstract: Neurons can release damaged mitochondria and transfer them to astrocytes for disposal and recycling. This ability to exchange mitochondria may represent a potential mode of cell-to-cell signalling in the central nervous system. Here we show that astrocytes in mice can also release functional mitochondria that enter neurons. Astrocytic release of extracellular mitochondrial particles was mediated by a calcium-dependent mechanism involving CD38 and cyclic ADP ribose signalling. Transient focal cerebral ischaemia in mice induced entry of astrocytic mitochondria into adjacent neurons, and this entry amplified cell survival signals. Suppression of CD38 signalling by short interfering RNA reduced extracellular mitochondria transfer and worsened neurological outcomes. These findings suggest a new mitochondrial mechanism of neuroglial crosstalk that may contribute to endogenous neuroprotective and neurorecovery mechanisms after stroke.
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Elga
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.|Cerebrovascular Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wang
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Terasaki
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.|Cerebrovascular Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Changhong
authors.initials: C
authors.lastname: Xing
authors.affiliation: Cerebrovascular Research Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Xunming
authors.initials: X
authors.lastname: Ji
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D036563:Cyclic ADP-Ribose / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D065840:Protective Factors; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013312:Stress, Physiological; D020521:Stroke / Q000378:metabolism / Q000473:pathology*
chemical_list: D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D036563:Cyclic ADP-Ribose; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium