Mitochondrial Transfer from Astrocytes to Neurons following Ischemic Insult: Guilt by Association?  Michael V. Berridge, Remy T. Schneider, Melanie J. McConnell  Cell Metabolism  Volume 24, Issue 3, Pages 376-378 (September 2016) DOI: 10.1016/j.cmet.2016.08.023 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Mitochondrial Transfer from Astrocytes to Neurons: Transfer or Guilt by Association? Potential mechanisms for the transfer of membrane-bound particles containing mitochondria between astrocytes (red) and neurons (green) damaged by glucose-oxygen deprivation are depicted. (A) Neurotrophic support by astrocytes has been shown to include transmitophagy of defective mitochondria from the soma of neurons to adjacent astrocytes, with involvement of the lysosomal pathway of degradation (Davis et al., 2014). (B) Damaged neurons may also endocytose astrocyte-derived membrane-bound particles containing functional mitochondria. In this case, escape from the lysosomal pathway and release from the vesicle would be necessary for the transferred mitochondria to provide bioenergetic benefit to the compromised neuron. (C–E) Several mechanisms of particle association with damaged neurons may also exist. (C) Weak mitovesicle association with the damaged neuron. (D) Strong mitovesicle association with the damaged neuron. A mitovesicle fused with the plasma membrane expels mitochondria into the recipient cell. After mitochondrial transfer, retrograde signaling between the recipient cell nucleus and donor astrocyte likely precedes mitochondrial transfer, mtDNA replication and biogenesis, and any integration into the neuronal mitochondrial network. (E) A gap junction-mediated mitoparticle docks with the plasma membrane, resulting in channel formation and diffusion of small molecules via Connexin 43 hemichannels present on the astrocyte mitoparticle and neuronal plasma membrane. The myelin sheath of the axon is shown in blue. Cell Metabolism 2016 24, 376-378DOI: (10.1016/j.cmet.2016.08.023) Copyright © 2016 Elsevier Inc. Terms and Conditions