Final Report Summary - MITOSKELETON (Elucidating the Roles of Proteins of Mitochondrial DNA Maintenance)
Mitochondrial DNA (mtDNA) is essential for life, as it contributes key elements of the oxidative phosphorylation system, which provides most of the cell’s energy. Although mtDNA is distinct from nuclear DNA it is wholly dependent on nuclear encoded gene products for its maintenance and expression. Mitochondrial DNA, like DNA elsewhere, is not naked but organized in nucleoprotein complexes, or nucleoids. The protein components of mitochondrial nucleoids play roles in mtDNA protection, propagation, segregation and expression. They include two elements of the actin cytoskeleton beta-actin and non-muscle myosin heavy chain IIA (NM-IIA). The beta-actin in mitochondria is located in the mitochondrial matrix, where it associates primarily with mtDNA, as a monomer or small oligomer. Targeting of an actin-interacting protein to mitochondria causes nucleoid enlargement, which may be related to persistent interaction of mitochondrial ribosomes with the mitochondrial nucleoid. Especially as, we have also found that NMIIA and NMIIB have a regulatory role in mitochondrial protein synthesis. Therefore, beta-actin and the non-muscle myosin proteins in mitochondria are predicted to contribute to achieving a balance between mtDNA replication and mitochondrial expression.