Mito­chon­dr­ial Redox Biology

Mito­chon­dr­ial Free Rad­i­cal The­ory of Aging not ade­quate to explain effects of age and rever­sal of dys­func­tion. The focus on oxida­tive dam­age and free rad­i­cal scav­eng­ing in the analy­sis of the Mito­chon­dria Free Rad­i­cal The­ory of Aging (MFRTA) is not ade­quate to test the role of oxida­tive stress in aging. Our recent papers demon­strate a dynamic inter­ac­tion between oxi­dants and mito­chon­dr­ial ener­get­ics that 1) are depen­dent on the inter­ac­tion between the mito­chon­dria and cell envi­ron­ment, and 2) can­not be explained by the tra­di­tional view of oxida­tive dam­age. Cel­lu­lar oxi­dants play an impor­tant role in cell sig­nal­ing through their inter­ac­tion with the redox buffer­ing sys­tem and mod­i­fi­ca­tion of pro­tein thiol groups. This sys­tem, com­pris­ing the metabo­lites, GSH and NADPH and enzymes such as thiore­dox­ins, per­ox­ire­dox­ins, and glutare­dox­ins among oth­ers, exists in both the mito­chon­dria and cytoso­lic com­part­ments and is respon­si­ble for sens­ing and respond­ing to changes in the redox sta­tus of the cell. Com­mu­ni­ca­tion between the redox buffer­ing sys­tems and cel­lu­lar phys­i­ol­ogy pri­mar­ily occurs through reversible post-translational mod­i­fi­ca­tions of pro­tein thi­ols, includ­ing S-glutathionylation (PSSG), sulfeny­la­tion, and S-nitrosylation. One area of focus of our research is attempt­ing to under­stand the inter­ac­tion mito­chon­dr­ial func­tion, redox biol­ogy, and the thiol pro­teome in health and disease.

Redox Biology