The Role of ATAD3A and SLC25 Proteins in OPA1 Function

Abstract

OPA1 regulates cristae structure and mitochondrial DNA (mtDNA) maintenance. Recently, our lab identified ATAD3A and SLC25 proteins as OPA1 interactors. After validating these interactions by co-immunoprecipitation, the role of these proteins in OPA1 function was examined. Previously, ATAD3A was implicated in mtDNA maintenance. However, no change in mtDNA content or nucleoid number was observed in my studies following long-term and short-term ATAD3A knockdown suggesting that OPA1 maintains mtDNA independently of ATAD3A. Previous data from our lab demonstrates that OPA1 oligomerization and cristae structure is altered by nutrients. SLC25 proteins transport nutrients into mitochondria. Therefore, OPA1 oligomerization and cristae structure was analyzed following SLC25 protein inhibition and knockdown. Decreased OPA1 oligomerization and cristae remodeling was observed following SLC25 protein inhibition and OGC knockdown. In addition these changes correlate with decreased ATP synthase monomers and oligomers suggesting that cristae remodeling may affect metabolism. Overall, these studies enhance our understanding of OPA1 function.