Mitochondrial fragmentation enables localized signaling required for cell repair

Plasma membrane injury can cause lethal influx of calcium, but cells survive by mounting a polarized repair response targeted to the wound site. Mitochondrial signaling within seconds after injury enables this response. However, as mitochondria are distributed throughout the cell in an interconnecte...

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Bibliographic Details
Published in:	The Journal of cell biology 2020-05, Vol.219 (5)
Main Authors:	Horn, Adam, Raavicharla, Shreya, Shah, Sonna, Cox, Dan, Jaiswal, Jyoti K
Format:	Article
Language:	eng
Subjects:	Animals Apoptosis - genetics Calcium Calcium (mitochondrial) Calcium - metabolism Calcium influx Calcium Signaling - drug effects Calcium Signaling - genetics Cell death Cell Membrane - genetics Cell Membrane - pathology Cell Signaling Cell survival Damage localization Dynamins - genetics Fibroblasts Fission Humans Injury prevention Membranes Mice Microtubule-Associated Proteins - genetics Mitochondria Mitochondria - genetics Mitochondria - pathology Mitochondrial Dynamics - genetics Mitochondrial Proteins - genetics Organelles Peptide Elongation Factors - genetics Physiology Plasma Repair Signal Transduction - genetics Signaling Wound healing
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Summary:	Plasma membrane injury can cause lethal influx of calcium, but cells survive by mounting a polarized repair response targeted to the wound site. Mitochondrial signaling within seconds after injury enables this response. However, as mitochondria are distributed throughout the cell in an interconnected network, it is unclear how they generate a spatially restricted signal to repair the plasma membrane wound. Here we show that calcium influx and Drp1-mediated, rapid mitochondrial fission at the injury site help polarize the repair response. Fission of injury-proximal mitochondria allows for greater amplitude and duration of calcium increase in these mitochondria, allowing them to generate local redox signaling required for plasma membrane repair. Drp1 knockout cells and patient cells lacking the Drp1 adaptor protein MiD49 fail to undergo injury-triggered mitochondrial fission, preventing polarized mitochondrial calcium increase and plasma membrane repair. Although mitochondrial fission is considered to be an indicator of cell damage and death, our findings identify that mitochondrial fission generates localized signaling required for cell survival.
ISSN:	0021-9525 1540-8140