Recombinant human mitochondrial transcription factor A stimulates mitochondrial biogenesis and ATP synthesis, improves motor function after MPTP, reduces oxidative stress and increases survival after endotoxin

Recombinant human mitochondrial transcription factor A protein (rhTFAM) was evaluated for its acute effects on cultured cells and chronic effects in mice. Fibroblasts incubated with rhTFAM acutely increased respiration in a chloramphenicol-sensitive manner. SH-SY5Y cells showed rhTFAM concentration-dependent reduction of methylpyridinium (MPP+)-induced oxidative stress and increases in lowered ATP levels and viability. Mice treated with weekly i.v. rhTFAM showed increased mitochondrial gene copy number, complex I protein levels and ATP production rates; oxidative damage to proteins was decreased ~ 50%. rhTFAM treatment improved motor recovery rate after treatment with MPTP and dose-dependently improved survival in the lipopolysaccharide model of endotoxin sepsis.