The long-term goal of the proposed research is to understand the? mechanisms of regulation of mitochondrial biogenesis in Saccharomyces? cerevisiae. First, we will elucidate the functions of a putative ATP-? dependent RNA helicase in mitochondria encoded by the nuclear suv3 gene.? Suv3 is involved in various post-transcriptional activities in? mitochondria, and is essential for maintenance of the wild-type? mitochondrial genome. The properties of a mutant allele of sur3, call? SUV3-1, suggests that suv3 functions in group I intron splicing, and in? particular, to resolve excised group I introns from ribonucleoprotein? (RNP) splicing complexes. This model will be tested, including the? notion that SUV3-1 is a compromised RNA helicase. These studies will be? extended to characterize group I intron RNP complexes, with initial? emphasis on an 18S ribonucleoprotein particle containing the excised? omega intron of the 21S rRNA gene. Using strains with an intronless? wild-type mitochondrial genome, we will initiate studies to determine? other functions of suv3 in mitochondrial RNA metabolism. Our second? objective is to characterize a novel regulatory path we discovered called? retrograde regulation, whereby the functional state of mitochondria can? profoundly affect nuclear gene expression. We have proposed, and provided? evidence supporting the idea, that retrograde regulation is a mechanisms? for the cell to adjust to changes in mitochondrial function, biogenesis? and inheritance. We wish to elucidate the mechanisms of signaling from? mitochondria to the nucleus. Here, we will focus on two novel genes,? RTG1 that encodes a new member of the basic helix-loop-helix (bHLH)? family of transcription factors, and RTG2 that encodes a protein of? unknown function. The products of both genes are required for retrograde? regulation of the CIT2 gene, which encodes a peroxisomal isoform of? citrate synthase that functions as part of the glyoxylate cycle.? Retrograde regulation of CIT2 functions metabolically to provide citrate? to mitochondria from the glyoxylate cycle under conditions where the TCA? cycle may be limiting.
Our aims are to 1) determine how the bHLH? protein, RTG1, acts as a transcriptional switch for retrograde? regulation; 2) determine the function of RTG2; 3) define through genetics? and molecular approaches additional components of the retrograde pathway;? and 4) elucidate the blocks in metabolic communication between the TCA? and glyoxylate cycles in rtg1 and rtg2 mutants. These experiments should? provide additional insights into the function of retrograde regulation.?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Method to Extend Research in Time (MERIT) Award (R37)
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Poodry, Clifton A
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University of Texas Sw Medical Center Dallas
Schools of Medicine
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