Mitochondrial ‘kiss-and-run’: interplay between mitochondrial motility and fusion–fission dynamics

Abstract

Visualizing mitochondrial fusion in real time, we identified two classes of fusion events in mammalian cells. In addition to complete fusion, we observed transient fusion events, wherein two mitochondria came into close apposition, exchanged soluble inter-membrane space and matrix proteins, and re-separated, preserving the original morphology. Transient fusion exhibited rapid kinetics of the sequential and separable mergers of the outer and inner membranes, but allowed only partial exchange of integral membrane proteins. When the inner membrane fusion protein Opa1 level was lowered or was greatly elevated, transient fusions could occur, whereas complete fusions disappeared. Furthermore, transient fusions began from oblique or lateral interactions of mitochondria associated with separate microtubules, whereas complete fusions resulted from longitudinal merging of organelles travelling along a single microtubule. In contrast to complete fusion, transient fusions both required and promoted mitochondrial motility. Transient fusions were also necessary and sufficient to support mitochondrial metabolism. Thus, Opa1 expression and cytoskeletal anchorage govern a novel form of fusion that has a distinct function in mitochondrial maintenance.

Principles of the mitochondrial fusion and fission cycle in neurons

“…In turn, lower motility decreases the number of contacts and the fusion rate. The latter conclusion is consistent with previous findings that inhibition of mitochondrial movement by nocodazol and vasopressin in H9c2 cells also inhibited mitochondrial fusion (Liu et al, 2009). Similarly, a recent study by Twig et al suggested that mitochondrial motility facilitates mitochondrial fusion in H9c2 and INS1 cells (Twig et al, 2010).…”

Iron and Porphyrin Trafficking in Heme Biogenesis

“…This "kissand-run" mechanism would provide an efficient means for delivering iron to mitochondria in RBCs, which generate vast amounts of heme. Recent evidence showed that mitochondria fuse with each other and with the endoplasmic reticulum (21,22). Small organic compounds or some proteins may also bind free cellular iron (23).…”

Mitofusins ‘bridge’ the gap between oxidative stress and mitochondrial hyperfusion

“…Fission allows distribution of mitochondria to daughter cells following mitosis. Small mitochondria are more efficiently tracked along the cytoskeleton , which also allows a quality control mechanism to exist where fragmented 'old' mitochondria can be turned over by autophagy [2]. Fusion enables mitochondrial contents to be mixed between neighbouring organelles.…”