The mitochondrial unfolded protein response (UPRmt) is a pathway that is activated during times of mitochondrial dysfunction and is regulated by the transcription factor ATFS-1 (Activating Transcription Factor associated with Stress-1). During periods of mitochondrial dysfunction, mitochondrial import efficiency is decreased allowing ATFS-1 to traffic to the nucleus via its nuclear localization signal (NLS). Nuclear ATFS-1 then activates a cytoprotective transcriptional response that alleviates the mitochondrial dysfunction. Our objective was to identify other candidate transcription factors that act as regulators of UPRmt gene expression. Previous work identified seven transcription factors that are either induced during mitochondrial dysfunction or have been found to physically interact with ATFS-1 in vitro. An initial RNA interference (RNAi) screening was performed against these transcription factors in the clk-1(qm150) background, a mitochondrial stress mutant background that results in activation of the UPRmt. From these candidates, ZIP-5 was identified as a transcription factor required for UPRmt activation. RNAi against zip-5 resulted in reduced levels of the UPRmt reporter transgene hsp-60::GFP in the clk-1(qm150) mutant background. Interestingly, loss of function of ZIP-5 also suppresses the slowed growth phenotype, which is characteristic of mitochondrial stress animals. We hypothesize that ZIP-5 may act as a negative regulator of electron transport chain gene expression (ETC genes), which would allow zip-5 loss of function mitochondrial stressed animals to grow at a faster rate due to increased respiration rates. To verify this hypothesis, we used a respiration assay to measure oxygen consumption and quantitative RT-PCR to measure changes in mitochondrial- and nuclear-encoded electron transport chain gene expression in zip-5 mutant animals compared to wild-type. Thus, our observations provide preliminary evidence that ZIP-5 is a component of a mitochondrial protective transcriptional network, acting as negative regulator of mitochondrial biogenesis.

Elucidating a mitochondrial protective transcriptional network

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.