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Full-Text Articles in Pathology
Dysregulation Of Mitochondrial Ca2+ Uptake And Sarcolemma Repair Underlie Muscle Weakness And Wasting In Patients And Mice Lacking Micu1, Valentina Debattisti, Adam Horn, Raghavendra Singh, Erin L. Seifert, Marshall W. Hogarth, Davi A. Mazala, Kai Ting Huang, Rita Horvath, Jyoti K. Jaiswal, György Hajnóczky
Dysregulation Of Mitochondrial Ca2+ Uptake And Sarcolemma Repair Underlie Muscle Weakness And Wasting In Patients And Mice Lacking Micu1, Valentina Debattisti, Adam Horn, Raghavendra Singh, Erin L. Seifert, Marshall W. Hogarth, Davi A. Mazala, Kai Ting Huang, Rita Horvath, Jyoti K. Jaiswal, György Hajnóczky
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Muscle function is regulated by Ca2+, which mediates excitation-contraction coupling, energy metabolism, adaptation to exercise, and sarcolemmal repair. Several of these actions rely on Ca2+ delivery to the mitochondrial matrix via the mitochondrial Ca2+ uniporter, the pore of which is formed by mitochondrial calcium uniporter (MCU). MCU's gatekeeping and cooperative activation are controlled by MICU1. Loss-of-protein mutation in MICU1 causes a neuromuscular disease. To determine the mechanisms underlying the muscle impairments, we used MICU1 patient cells and skeletal muscle-specific MICU1 knockout mice. Both these models show a lower threshold for MCU-mediated Ca2+ uptake. Lack of …
Spg7 Targets The M-Aaa Protease Complex To Process Mcu For Uniporter Assembly, Ca2 Influx, And Regulation Of Mitochondrial Permeability Transition Pore Opening, Stephen Hurst, Ariele Baggett, György Csordás, Shey-Shing Sheu
Spg7 Targets The M-Aaa Protease Complex To Process Mcu For Uniporter Assembly, Ca2 Influx, And Regulation Of Mitochondrial Permeability Transition Pore Opening, Stephen Hurst, Ariele Baggett, György Csordás, Shey-Shing Sheu
Center for Translational Medicine Faculty Papers
The mitochondrial matrix ATPase associated with diverse cellular activities (m-AAA) protease spastic paraplegia 7 (SPG7) has been recently implicated as either a negative or positive regulatory component of the mitochondrial permeability transition pore (mPTP) by two research groups. To address this controversy, we investigated possible mechanisms that explain the discrepancies between these two studies. We found that loss of the SPG7 gene increased resistance to Ca2-induced mPTP opening. However, this occurs independently of cyclophilin D (cyclosporine A insensitive) rather it is through decreased mitochondrial Ca2 concentrations and subsequent adaptations mediated by impaired formation of functional mitochondrial Ca …
Intracellular Ca 2+ Sensing: Role In Calcium Homeostasis And Signaling, Rafaela Bagur, György Hajnóczky
Intracellular Ca 2+ Sensing: Role In Calcium Homeostasis And Signaling, Rafaela Bagur, György Hajnóczky
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Ca2+ is a ubiquitous intracellular messenger that controls diverse cellular functions but can become toxic and cause cell death. Selective control of specific targets depends on spatiotemporal patterning of the calcium signal and decoding it by multiple, tunable, and often strategically positioned Ca2+-sensing elements. Ca2+ is detected by specialized motifs on proteins that have been biochemically characterized decades ago. However, the field of Ca2+ sensing has been reenergized by recent progress in fluorescent technology, genetics, and cryo-EM. These approaches exposed local Ca2+-sensing mechanisms inside organelles and at the organellar interfaces, revealed how Ca …
The Role Of Calcium Ions In Toxic Cell Injury., John L. Farber
The Role Of Calcium Ions In Toxic Cell Injury., John L. Farber
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Calcium ions have been increasingly implicated as a mediator of the mechanisms generating lethal cell injury under a variety of pathologic circumstances. An overview of the various roles suggested for such alterations in cellular calcium homeostasis is presented. The central role of plasma membrane damage in the genesis of irreversible cell injury is used to divide the postulated roles for calcium ions into two major mechanisms. On the one hand, calcium ions have been proposed as mediators of the functional consequences of plasma membrane injury. An influx of extracellular calcium ions across a damaged permeability barrier and down a steep …