Fig. 3: Terminology to describe mitochondria transfer.

a, Vertical inheritance of mitochondria occurs during cell division to pass on mitochondria to daughter cells. Horizontal or intercellular mitochondria transfer occurs in the absence of cell division and may occur between developmentally distinct cell types. b, The cell of origin is known as the donor cell, and the cells that obtain the transferred mitochondria are known as acceptor cells. When the donor and acceptor cells are defined in vivo, this is referred to as a mitochondria transfer axis. c, A mitochondria transfer network is the co-occurrence of multiple mitochondria transfer axes in parallel or in series. d, Interorgan mitochondria transfer occurs when cells in one organ release their mitochondria into a circulating body fluid, such as blood, for delivery to cells in another organ. e, Contact-dependent mechanisms of mitochondria transfer. Tunnelling nanotube-mediated mitochondria transfer occurs when two or more cells form connections that permit direct delivery of mitochondria from the cytoplasm of one cell to that of another. Dendritic structure-mediated mitochondria transfer is a process in which one cell extends a tubular structure that makes contact to acceptor cell via end feet. The cytoplasms of the two cells are not directly connected, as is the case with tunnelling nanotubes. Adhesion-mediated mitochondria transfer occurs when two cells make direct physical contact, sometimes mediated by a gap junctional channel such as Cx43. The mitochondria are transferred to the acceptor cell not via the channel pore, which is too small to permit passage of large cargo, but by an endocytic mechanism at the cell-to-cell interface. f, Contact-independent mechanisms of mitochondria transfer. Donor cells can release mitochondria into the extracellular space in various forms, and these can then be imported by acceptor cells. All these forms can be referred to as extracellular mitochondria (ex-Mito). One subset of ex-Mito is known as free mitochondria, which are not enclosed within an extracellular vesicle (EV). There are several subsets of EVs containing mitochondria (EV-Mito) that differ based on their size, type of mitochondrial cargo, and mechanisms of release. Cargo can include intact mitochondria or mitochondria-derived vesicles (MDVs). The mechanisms that regulate the release and uptake of ex-Mito remain the subject of ongoing investigation.