Mitochondria‐targeted Probes and Functional Molecules

Our research aims to use chemical biology to understand processes associated with mitochondria, including their role in oxidative stress and in the control of muscle contraction. The advantage of chemical biology is that probes and functional molecules developed can in theory be used in any cell type, tissue or organism. The design, validation and application of molecules targeted to the mitochondrial matrix with a lipophilic cation and designed to respond to an internal or external stimulus will be explained. Three types of probe will be discussed: (a) a mitochondria‐targeted probe, MitoB, which accumulates in mitochondria, reacts selectively with hydrogen peroxide, and can be used to assess oxidative stress in the mitochondria of whole organisms; (b) functional molecules that sense hydrogen peroxide and respond by releasing an uncoupler that moderates the potential across the mitochondrial inner membrane, and are designed to test aspects of the free radical theory of aging; (c) a mitochondria‐targeted photoactivatable uncoupler, which allows individual mitochondria in native smooth muscle cells to be “switched off” at will. The research is multidisciplinary and involves a large number of co‐workers, collaborators and funders, who will be acknowledged in the talk. Main funders: the Wellcome Trust, BBSRC (SPARC), Royal Society of Edinburgh and TSB