University of Louisville

New trick for an old dog - Mitofusin controls peroxisomal dynamics in stem cells

Grade Level at Time of Presentation

Freshmen

Major

Neurobiology

2nd Grade Level at Time of Presentation

Senior

2nd Student Major

Biology

2nd Student Minor

Psychology

Department

Dept. of Biology

Abstract

Adult stem cells make up an important reservoir of progenitor cells capable regenerating tissues and organs throughout lifetime. Several signaling pathways have been characterized to influence the decision stem cells make between self-renewing (i.e., maintaining themselves) and differentiating into specialized cells. Recent evidence emerged to show that changes in metabolism can also influence stem cell behavior. For instance, in the fruit fly Drosophila melanogaster, male germline stem cells (GSCs) rely on mitochondrial fatty acid metabolism for their maintenance. Depletion of the mitochondrial fusion factor Mitofusin caused mitochondria not only to not fuse, but also lose their function and impair fatty acid oxidation. Mitochondria can oxidize short and medium chain fatty acids for their catabolism. However, branched and very long chain fatty acids must first be catabolized in peroxisomes.

Unexpectedly, we observed that peroxisomes also partially lost their function when Mitofusin was depleted in GSCs, as assayed by the incorporation of the peroxisomal marker SKL2:GFP. We are currently investigating 1) if this is specific to GSCs or also happens in other cell types and 2) if Mitofusin is directly controlling peroxisomal function or if this is an indirect impact in peroxisomes after mitochondrial loss of function.

Given that Mitofusins have not been previously linked to peroxisomal function, these results could potentially help us better understand the interplay between metabolic organelles, and whether diseases linked to mutations in Mitofusin can be ameliorated by the rescue of peroxisomal function.

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New trick for an old dog - Mitofusin controls peroxisomal dynamics in stem cells

Adult stem cells make up an important reservoir of progenitor cells capable regenerating tissues and organs throughout lifetime. Several signaling pathways have been characterized to influence the decision stem cells make between self-renewing (i.e., maintaining themselves) and differentiating into specialized cells. Recent evidence emerged to show that changes in metabolism can also influence stem cell behavior. For instance, in the fruit fly Drosophila melanogaster, male germline stem cells (GSCs) rely on mitochondrial fatty acid metabolism for their maintenance. Depletion of the mitochondrial fusion factor Mitofusin caused mitochondria not only to not fuse, but also lose their function and impair fatty acid oxidation. Mitochondria can oxidize short and medium chain fatty acids for their catabolism. However, branched and very long chain fatty acids must first be catabolized in peroxisomes.

Unexpectedly, we observed that peroxisomes also partially lost their function when Mitofusin was depleted in GSCs, as assayed by the incorporation of the peroxisomal marker SKL2:GFP. We are currently investigating 1) if this is specific to GSCs or also happens in other cell types and 2) if Mitofusin is directly controlling peroxisomal function or if this is an indirect impact in peroxisomes after mitochondrial loss of function.

Given that Mitofusins have not been previously linked to peroxisomal function, these results could potentially help us better understand the interplay between metabolic organelles, and whether diseases linked to mutations in Mitofusin can be ameliorated by the rescue of peroxisomal function.