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Indeed, Duchenne muscular dystrophy (MD) is driven by dysfunctional Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx across the sarcolemma that causes mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    overload, organelle rupture, and muscle necrosis. The mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    uniporter (MCU) complex is the primary characterized mechanism for acute mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    uptake. One strategy for preventing mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    overload is deletion of the\n                    <jats:italic>Mcu<\/jats:italic>\n                    gene, the pore forming subunit of the MCU-complex. Conversely, enhanced MCU-complex Ca\n                    <jats:sup>2+<\/jats:sup>\n                    uptake is achieved by deleting the inhibitory\n                    <jats:italic>Mcub<\/jats:italic>\n                    gene. Here we show that myofiber-specific\n                    <jats:italic>Mcu<\/jats:italic>\n                    deletion was not protective in a mouse model of Duchenne MD. Specifically,\n                    <jats:italic>Mcu<\/jats:italic>\n                    gene deletion did not reduce muscle histopathology, did not improve muscle function, and did not prevent mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    overload. Moreover, myofiber specific\n                    <jats:italic>Mcub<\/jats:italic>\n                    gene deletion did not augment Duchenne MD muscle pathology. Interestingly, we observed MCU-independent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    uptake in dystrophic mitochondria that was sufficient to drive mitochondrial permeability transition pore (MPTP) activation and skeletal muscle necrosis, and this same type of activity was observed in heart, liver, and brain mitochondria. These results demonstrate that mitochondria possess an uncharacterized MCU-independent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    uptake mechanism that is sufficient to drive MPTP-dependent necrosis in MD in vivo.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-57340-3","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T03:01:51Z","timestamp":1710990111000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["MCU-independent Ca2+ uptake mediates mitochondrial Ca2+ overload and necrotic cell death in a mouse model of Duchenne muscular dystrophy"],"prefix":"10.1038","volume":"14","author":[{"given":"Michael J.","family":"Bround","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eaman","family":"Abay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuzhou","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian R.","family":"Havens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen J.","family":"York","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald M.","family":"Bers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"57340_CR1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.yjmcc.2022.11.003","volume":"174","author":"DJ Robichaux","year":"2023","unstructured":"Robichaux, D. 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