Metabolomic profiling rationalized pyruvate efficacy in cybrid cells harboring MELAS mitochondrial DNA mutations

Pyruvate treatment was found to alleviate clinical symptoms of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome and is highly promising therapeutic. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we measured time-changes of 161 intracellular and 85 medium metabolites to elucidate metabolic effects of pyruvate treatment on cybrid human 143B osteosarcoma cells harboring normal (2SA) and MELAS mutant (2SD) mitochondria. The results demonstrated dramatic and sustainable effects of pyruvate administration on the energy metabolism of 2SD cells, corroborating pyruvate as a metabolically rational treatment regimen for improving symptoms associated with MELAS and possibly other mitochondrial diseases.

► Metabolome analysis rationalized pyruvate efficacy in MELAS Grand Conference Hall, Seoul Olympic Parktel mutant 2SD cells.
► 2SD cells showed high [NADH]/[NAD], constantly low ATP, and poor energy status.
► Pyruvate treatment improved energy status of 2SD cells by improving [NADH]/[NAD].
► Alanine and TCA cycle intermediates increased in 2SD cells by pyruvate treatment.
► Pyruvate is a promising remedy for MELAS and possibly other mitochondrial diseases.