Madesh Muniswamy, M.S., PhD

Long Endowed Tenured Professor in Medicine

Personal Statement:

Mitochondrial metabolism in health and disease, ion channels, oxidative stress, molecular signaling research

My laboratory is an integrated molecular, cell and biochemistry laboratory studying mitochondrial physiology, calcium signaling, and redox biology in cell function. Our recent discovery demonstrated that a mitochondrial resident transmembrane protein Mitochondrial Ca2+ Uniporter Regulator 1 (MCUR1) is essential for Mitochondrial Ca2+ Uniporter (MCU)-mediated mitochondrial Ca2+ uptake (Nature Cell Biology 2012; Highlights Nature Reviews Molecular Cell Biology, Cell Reports 2016). In another study, we identified the molecular component (Mitochondrial Ca2+ Uptake 1; MICU1) that controls mitochondrial Ca2+ uptake “set-point” a concept known over thirty years (Cell 2012 and Cell Reports 2013). These components were unknown for over five decades. MICU1 and MCUR1 negatively and positively control the mitochondrial Ca2+ uniporter pore submit (MCU) activity under resting and active state, respectively. MCU interacts with MICU1 and MCUR1 independently and forms MCU complex in the mitochondrial inner membrane. Dysregulation of mitochondrial Ca2+ uptake have been linked to numerous cellular dysfunction including chronic oxidative burden, autophagy and sensitization for cell death (Science Signaling 2015). Therefore, it is reasonable to speculate that [Ca2+]m overload in environmental stress conditions could lead to increased mROS levels, thereby altering proliferation and differentiation.

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