ULP-4 desumoylates HMGS-1 to regulate C. elegans bioenergetics in aging and development


Kaitlin Ching


  • Paul Sternberg, Thomas Hunt Morgan Professor of Biology, California Institute of Technology
  • Amir Sapir, Postdoctoral Fellow, California Institute of Technology

Molecular circuits by which metabolic networks cope with aging and mitochondrial stress have yet to be well understood, but their regulatory methods are important to everyday health, cholesterol production, mitochondrial disease, and potentially cancer treatment. We hypothesize that post-transcriptional modifications of key metabolic proteins play a role in this regulation. Here, we demonstrate that ubiquitin-like protease 4 (ULP-4) regulates mitochondrial homeostasis and C. elegans bioenergetics during development and aging by desumoylating HMG-CoA synthase (HMGS-1). This was determined by staining, lifespan, and respiration assays in the nematode Caenorhabditis elegans. Mitochondrial staining shows a diminished electrochemical gradient in ulp-4 mutants, suggesting that the electron transport chain (ETC) is impaired in the absence of ULP-4. Life span extension and decreased oxygen consumption similarly indicate impaired mitochondrial activity in ulp-4 mutants. RNAi knock-down of hmgs-1 results in phenotypes similar to ulp-4 knock-out; hence the previously observed interactions between HMGS-1 and ULP-4 are likely positive. The mevalonate pathway, in which HMGS-1 plays a major role, produces coenzyme Q which shuttles electrons through the ETC. Our results support a model in which, by regulating HMGS-1 activity, ULP-4 impacts the ETC. By unveiling the role of ulp-4 in mitochondrial regulation, we hope to better understand the how metabolic networks are regulated during development and aging.

Presented by:

Kaitlin Ching


Saturday, November 23, 2013


1:55 PM — 2:10 PM


Science 204

Presentation Type:

Oral Presentation