Abstract:
Mitochondria have an important role in cell metabolism, being the major site of ATP
production via oxidative phosphorylation (OXPHOS). Accumulation of mtDNA
mutations have been linked to the development of respiratory dysfunction, apoptosis, and
aging. Base excision repair (BER) is the major and the only certain repair pathway
existing in mitochondria that is in responsible for removing and repairing various base
modifications as well as abasic sites (AP sites). In this research, Saccharomyces
cerevisiae (S. cerevisiae) BER gene knockout strains, including 3 single DNA
glycosylase gene knockout strains and Ap endonuclease (Apn 1 p) knockout strain were
used to examine the importance of this DNA repair pathway to the maintenance of
respiratory function. Here, I show that individual DNA glycosylases are nonessential in
maintenance of normal function in yeast mitochondria, corroborating with previous
research in mammalian experimental models. The yeast strain lacking Apn 1 p activity
exhibits respiratory deficits, including inefficient and significantly low intracellular ATP
level, which maybe due to partial uncoupling of OXPHOS. Growth of this yeast strain on
respiratory medium is inhibited, but no evidence was found for increased ROS level in
Apn 1 p mitochondria. This strain also shows an increased cell size, and this observation
combined with an uncoupled OXPHOS may indicate a premature aging in the Apnlp
knockout strain, but more evidence is needed to support this hypothesis. However, the
BER is necessary for maintenance of mitochondrial function in respiring S.cerevisiae.
