Mitochondrial oxidative damage and dysfunction contributes to a number of c
ell pathologies. To investigate how this damage affects cell function we ha
ve developed mitochondrially targeted antioxidants and thiol reagents by co
valently linking them to lipophilic cations. The cation drives the selectiv
e accumulation of these reagents into mitochondria within cells where the a
ntioxidants decrease oxidative damage and the thiol reagents enable measure
ment of the redox status of thiol proteins. In conjunction with cell and an
imal models of apoptosis, oxidative damage, and nitric oxide signaling, the
se molecules may provide new insights into the roles of mitochondria in hum
an pathologies. (C) 2000 Elsevier Science Inc.