Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease
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 m...
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doaj-fd0c136fa7fc450bb5f14c11899a52832020-11-25T00:53:07ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-01-0120228610.3390/ijms20020286ijms20020286Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and DiseaseQi-Tong Lin0Peter B. Stathopulos1Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, CanadaDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, CanadaMitochondrial 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.http://www.mdpi.com/1422-0067/20/2/286leucine zipperEF-handcoiled-coilLETM1LETM2calcium signalingNa+/K+ exchangerCa2+/H+ exchangerstructural mechanismWolf-Hirschhorn syndromecancermitochondria |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qi-Tong Lin Peter B. Stathopulos |
spellingShingle |
Qi-Tong Lin Peter B. Stathopulos Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease International Journal of Molecular Sciences leucine zipper EF-hand coiled-coil LETM1 LETM2 calcium signaling Na+/K+ exchanger Ca2+/H+ exchanger structural mechanism Wolf-Hirschhorn syndrome cancer mitochondria |
author_facet |
Qi-Tong Lin Peter B. Stathopulos |
author_sort |
Qi-Tong Lin |
title |
Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease |
title_short |
Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease |
title_full |
Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease |
title_fullStr |
Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease |
title_full_unstemmed |
Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease |
title_sort |
molecular mechanisms of leucine zipper ef-hand containing transmembrane protein-1 function in health and disease |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-01-01 |
description |
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. |
topic |
leucine zipper EF-hand coiled-coil LETM1 LETM2 calcium signaling Na+/K+ exchanger Ca2+/H+ exchanger structural mechanism Wolf-Hirschhorn syndrome cancer mitochondria |
url |
http://www.mdpi.com/1422-0067/20/2/286 |
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