AMPK-FOXO-IP3R signaling pathway mediates defects caused by mitochondrial DNA mutations

What is it about?

Mitochondria, the powerhouse of the cell, have their own genomes (mtDNA). Multiple human mitochondrial diseases, such as Leber hereditary optic neuropathy (LHON) and Leigh syndrome (LS), are caused by pathogenic mutations in mtDNA and exhibit a series of neurological, behavioral, and developmental defects such as visual and hearing loss, movement disorder, and cognitive defects. How mtDNA mutations lead to these deficiencies is poorly understood. By studying several different mtDNA mutations from the round worm Caenorhabditis elegans, researchers from the University of Colorado Boulder identify a signaling pathway, the AMPK (AMP-activated protein kinase)-FOXO (forkhead box class O transcription factors)-IP3R (inositol triphosphate receptor) pathway, important for mediating these defects. Importantly, vitamin MK-4 can remedy the deficiencies in these mtDNA mutant animals, providing a potential treatment strategy for the mitochondrial diseases.

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Why is it important?

Mitochondrial diseases can cause severe health problems and affect the quality of life of patients, but there is currently no effective treatment for these diseases. This study reveals key biomolecules and a signaling pathway that mediate neurological, behavioral, and developmental defects seen in mitochondrial diseases due to mutations in the mitochondrial genomes and discovers vitamin MK-4 as a potential therapeutic treatment for these diseases.