Abstract
Nearly 2 decades since its discovery as one of the genes responsible for the Wolf-Hirschhorn Syndrome (WHS), the primary function of the leucine-zipper EF-hand containing transmembrane 1 (LETM1) protein in the inner mitochondrial membrane (IMM) or the mechanism by which it regulates mitochondrial Ca2+ handling is unresolved. Meanwhile, LETM1 has been associated with the regulation of fundamental cellular processes, such as development, cellular respiration and metabolism, and apoptosis. This mini-review summarizes the diversity of cellular functions impacted by LETM1 and highlights the multiple roles of LETM1 in health and disease.
Highlights
Mitochondria accumulate large amounts of Ca2+ via highly regulated mechanisms of Ca2+ transport across the mitochondrial membranes and Ca2+ handling in the matrix (Rizzuto et al, 2012) and thereby, attenuate deleterious increases in cytosolic Ca2+ (Hajnóczky et al, 2014)
The Letm1 gene was originally identified as one of the genes deleted in patients afflicted with the Wolf-Hirschhorn Syndrome (WHS), a contiguous gene deletion disorder marked by severe growth and intellectual disability, hypotonia, and seizures (Endele et al, 1999; Schlickum et al, 2004)
Leucine zipper EF-hand containing transmembrane 1 (LETM1) has been shown to interact with proteins that regulate varied signaling processes, such as import and assembly of critical respiratory supercomplexes in the inner mitochondrial membrane (IMM), cellular glucose metabolism, and neuronal function (Figure 2)
Summary
Mitochondria accumulate large amounts of Ca2+ via highly regulated mechanisms of Ca2+ transport across the mitochondrial membranes and Ca2+ handling in the matrix (Rizzuto et al, 2012) and thereby, attenuate deleterious increases in cytosolic Ca2+ (Hajnóczky et al, 2014). LETM1 has been shown to interact with proteins that regulate varied signaling processes, such as import and assembly of critical respiratory supercomplexes in the IMM, cellular glucose metabolism, and neuronal function (Figure 2). In cells and isolated mitochondria, it is unclear whether LETM1-CHE mediates either mitochondrial Ca2+ uptake or efflux.
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