AI Article Synopsis
- Calcium uptake by mitochondria is crucial for managing energy levels, cell death, and calcium signals, and is primarily facilitated by the Mitochondrial Calcium Uniporter (MCU).
- Although the regulation of MCU by MICUs is well-established, the impact of divalent cations like magnesium (Mg) on MCU activity is less understood.
- The study identified Mrs2 as the mammalian mitochondrial Mg channel and demonstrated that lower matrix magnesium levels lead to increased MCU activity and calcium overload, ultimately contributing to cell death during tissue injury.
Article Abstract
Calcium (Ca) uptake by mitochondria is essential in regulating bioenergetics, cell death, and cytosolic Ca transients. Mitochondrial Calcium Uniporter (MCU) mediates the mitochondrial Ca uptake. MCU is a heterooligomeric complex with a pore-forming component and accessory proteins required for channel activity. Though MCU regulation by MICUs is unequivocally established, there needs to be more knowledge of whether divalent cations regulate MCU. Here we set out to understand the mitochondrial matrix Mg-dependent regulation of MCU activity. We showed Mrs2 as the authentic mammalian mitochondrial Mg channel using the planar lipid bilayer recordings. Using a liver-specific Mrs2 KO mouse model, we showed that decreased matrix [Mg] is associated with increased MCU activity and matrix Ca overload. The disruption of Mgdependent MCU regulation significantly prompted mitochondrial permeability transition pore opening-mediated cell death during tissue IR injury. Our findings support a critical role for mMg in regulating MCU activity and attenuating mCa overload.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371168 | PMC |
| http://dx.doi.org/10.21203/rs.3.rs-3088175/v1 | DOI Listing |
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