Transfer of mitochondria and endosomes between cells by gap junction internalization

Intercellular organelle transfer has been documented in several cell types and has been proposed to be important for cell‐cell communication and cellular repair. However, the mechanisms by which organelle transfer occurs are uncertain. Recent studies indicate that the gap junction protein, connexin 43 (Cx43), is required for mitochondrial transfer but its specific role is unknown. Using three‐dimensional electron microscopy and immunogold labeling of Cx43, this report shows that whole organelles including mitochondria and endosomes are incorporated into double‐membrane vesicles, called connexosomes or annular gap junctions, that form as a result of gap junction internalization. These findings demonstrate a novel mechanism for intercellular organelle transfer mediated by Cx43 gap junctions. Gap junctions play an undefined role in the transfer of mitochondria between cells. By visualizing immunogold‐labeled serial sections of intact tissue with scanning electron microscopy, organelles, including mitochondria and endosomes, are found within deeply invaginated gap junctions and in fully internalized gap junctions. This establishes gap junction internalization as a new mechanism for organelle transfer between cells.