Molecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue

► The TPP+-tagged vitamin E succinate (MitoVES) affected mitochondrial functions. ► MitoVES stimulated basal respiration and ATP hydrolysis in mitochondria. ► MitoVES inhibited OxPhos and Ca2 + uptake by collapsing the membrane potential in mitochondria. ► The respiratory complex II was the most sensitive MitoVES target. ► MitoVes potently inhibited OxPhos and induced ATP depletion in rodent and human cancer cells.