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2024年10月6日 星期日

Mitochondrial nanotunnels

Mitochondrial nanotunnels


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Mitochondrial nanotunnels are thin ~100-nm-wide double-membrane protrusions that arise from donor mitochondria, extend over distances up to several microns, and can interact and fuse with a receiver mitochondrion. Nanotunnels transport matrix proteins and therefore represent a mechanism of protein sharing and communication even between non-adjacent mitochondria. In cultured cells, nanotunnels can be induced by the pulling action of the kinesin motor protein Kif5b. In vivo, the existence of nanotunnels has been limited to tissues where mitochondrial motility is restricted such as in the densely packed cytoplasm of human skeletal muscles and rat cardiomyocytes, suggesting that physically constrained mitochondria that cannot encounter diverse fusion partners reach out to other functional mitochondria via nanotunnels. In patients with mitochondrial disease, mitochondria with compromised OxPhos function due to mtDNA mutations were found to have ~6-fold more nanotunnels than in healthy controls. This suggests that mitochondrial nanotunnels may preferentially arise or stabilize between mitochondria with impaired OxPhos capacity as a mean of functional complementation, or as a mean of increasing the effective functional connectivity among the mitochondrial network of the MIPS. Among other biological networks, enhancing the structural connectivity between individual units alters global network properties and can enhance robustness and computational/cognitive properties.

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