Student Presenter(s): Yllka Valdez
Faculty Mentor: Steve M Claypool
School/College: Arts and Sciences, Old Westbury

ADP/ATP carriers (Aac) are crucial for energy production in the mitochondria with a role in the proper functioning of oxidative phosphorylation (OXPHOS). Aac is located in the inner membrane of the mitochondrion and exchanges ADP into the matrix, and ATP out of the cytosol. Aac2 is the only isoform in yeast necessary for OXPHOS, relying on cardiolipin (CL), a phospholipid in the mitochondria. Findings of a patient show a missense mutation in ANT1, an isoform in mammalian Aac, affecting the functioning of the protein. This allele (ANT1L141F, corresponding to yeast Aac2L155F) indicates mitochondrial myopathy, estimated to reflect impairment of mitochondrial function. The patient mutation is located where Aac interacts with CL and yeast Aac2 carrying a glutamate point mutation at the corresponding position of the patient mutation (yAac2L155E) fails to interact with CL. We aimed to identify the pathological mechanism behind the patient mutation by comparing growth, expression, and structural folding status to the mutant. Results in the SDS PAGE/western blotting illustrated that the mutant is expressed similar to wildtype Aac2, thus the mutant Aac2 amount present is not a cause of defect. Blue native-PAGE showed that the structure of each Aac2 mutant was destabilized. The results suggest that disrupted interactions between Aac2 and CL result in destabilized structure, thus leading to mitochondrial dysfunction and human disease.