关键词: LETM1 Wolf–Hirschhorn syndrome calcium metabolism mitochondria potassium

Mesh : Calcium / metabolism Calcium-Binding Proteins / genetics metabolism Cations / metabolism Homeostasis Humans Membrane Proteins / genetics metabolism Mitochondria / metabolism Mitochondrial Proteins / genetics metabolism Models, Molecular Potassium / metabolism Protein Conformation Seizures / metabolism Signal Transduction Wolf-Hirschhorn Syndrome / metabolism

来  源:   DOI:10.1016/j.tibs.2019.04.002   PDF(Sci-hub)

Abstract:
Mitochondrial function is essential for life. Therefore, it is unsurprising that perturbations in mitochondrial function have wide-ranging consequences in the cell. High-throughput screening has identified essential genes required for cellular survival and fitness. One such gene is LETM1. The undisputed function of LETM1 from yeast to human is to maintain the mitochondrial osmotic balance. Osmotic imbalance has been demonstrated to affect mitochondrial morphology, dynamics, and, more recently, metabolism. Whether conservation of osmotic homeostasis by LETM1 occurs by extrusion of excess mitochondrial potassium (K+), calcium (Ca2+), or both has been a matter of dispute over the past 10 years. In this Opinion, we report and discuss recent findings on LETM1 structure, essentiality, and function and its involvement in Wolf-Hirschhorn syndrome (WHS) and seizures.
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