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Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease

Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada
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Int. J. Mol. Sci. 2019, 20(2), 286; https://doi.org/10.3390/ijms20020286
Received: 19 December 2018 / Revised: 8 January 2019 / Accepted: 9 January 2019 / Published: 12 January 2019
(This article belongs to the Special Issue Calcium Signaling in Human Health and Diseases 2.0)
Mitochondrial calcium (Ca2+) uptake shapes cytosolic Ca2+ signals involved in countless cellular processes and more directly regulates numerous mitochondrial functions including ATP production, autophagy and apoptosis. Given the intimate link to both life and death processes, it is imperative that mitochondria tightly regulate intramitochondrial Ca2+ levels with a high degree of precision. Among the Ca2+ handling tools of mitochondria, the leucine zipper EF-hand containing transmembrane protein-1 (LETM1) is a transporter protein localized to the inner mitochondrial membrane shown to constitute a Ca2+/H+ exchanger activity. The significance of LETM1 to mitochondrial Ca2+ regulation is evident from Wolf-Hirschhorn syndrome patients that harbor a haplodeficiency in LETM1 expression, leading to dysfunctional mitochondrial Ca2+ handling and from numerous types of cancer cells that show an upregulation of LETM1 expression. Despite the significance of LETM1 to cell physiology and pathophysiology, the molecular mechanisms of LETM1 function remain poorly defined. In this review, we aim to provide an overview of the current understanding of LETM1 structure and function and pinpoint the knowledge gaps that need to be filled in order to unravel the underlying mechanistic basis for LETM1 function. View Full-Text
Keywords: leucine zipper; EF-hand; coiled-coil; LETM1; LETM2; calcium signaling; Na+/K+ exchanger; Ca2+/H+ exchanger; structural mechanism; Wolf-Hirschhorn syndrome; cancer; mitochondria leucine zipper; EF-hand; coiled-coil; LETM1; LETM2; calcium signaling; Na+/K+ exchanger; Ca2+/H+ exchanger; structural mechanism; Wolf-Hirschhorn syndrome; cancer; mitochondria
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Lin, Q.-T.; Stathopulos, P.B. Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease. Int. J. Mol. Sci. 2019, 20, 286.

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