Saneto_2022_Front.Mol.Biosci_9_908721

Communication between intracellular organelles is essential for overall cellular function. How this communication occurs and under what circumstances alterations transpire are only the beginning to be elucidated. The pathways of calcium homeostasis, lipid transfer, mitochondrial dynamics, and mitophagy/apoptosis have been linked to the endoplasmic reticulum and tethering sites on the outer and/or inner mitochondrial membrane called mitochondria-associated endoplasmic reticulum membranes (MAM). Sensitive visualization by high-powered microscopy coupled with the advent of massive parallel sequencing has elaborated the structure, while patient's diseases have uncovered the physiological function of these networks. Using specific patient examples from our pediatric mitochondrial center, we expand how specific genetic pathological variants in certain MAM structures induce disease. Genetic variants in MICU1, PASC-2, CYP2U1, SERAC1, and TANGO2 can induce early development abnormalities in the areas of cognition, motor, and central nervous system structures across multiple MAM pathways and implicate mitochondrial dysregulation.