Collaborate 2 Cure
August 14, 2017
Location:

Enterprise Center of Johnson County (ECJC)
4220 Shawnee Mission Parkway, Suite 350B, Fairway, KS 66205

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Presentation Regulation of Multimeric PGAM5 Complexes and Their Role in Mitochondrial Dynamics

There is compelling evidence that the accumulation of dysfunctional mitochondria participate in neurodegenerative diseases. For example, loss of function mutations in genes that encode proteins involved in the mitophagic removal of dysfunctional mitochondria have been implicated in Parkinson’s Disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Our laboratory has identified an atypical protein phosphatase termed Phosphoglycerate Mutase family member 5 (PGAM5) as a novel interactor of the Keap1 ubiquitin ligase complex. PGAM5 regulates multiple aspects of mitochondrial function, including mitophagy. We have identified a highly conserved motif in PGAM5 that is critical for both the formation of multimeric complexes and for robust phosphatase activity, suggesting that formation of multimeric PGAM5 complexes is critical for the biological function of PGAM5. I will present recent data from our laboratory regarding how the formation of multimeric complexes of PGAM5 is regulated. The importance of PGAM5 multimeric complexes for mitochondrial dynamics will be discussed.

Speaker- Mark Hannink, PhD

Mark Hannink, Professor, Biochemistry Department, University of Missouri School of Medicine and the Bond Life Sciences Center. Dr. Hannink earned his PhD from the University of California, San Diego and was an American Cancer Society postdoctoral fellow at the University of Wisconsin. Dr. Hannink’s lab is interested in the response of cells to oxidative stress.

Effect of Oxaloacetate for the Motor Function and Life Span of Amyotrophic Lateral Sclerosis (ALS) Model Mice

Etiology of ALS has not been identified, however, it is thought that aggregates of disease-causing mutant proteins and RNAs disrupt the normal cellular functions. Mitochondrial dysfunction seems to play a major role in the pathology of ALS. These defects lead to dying back neuropathy and motor neuron degeneration. Therefore, restoration of mitochondria function is likely to cause beneficial effect for the survival of ALS model mice. Oxaloacetate has beneficial effect on mitochondria biogenesis. Oxaloacetate can access central nervous system by systemic administration, is neuroprotective in neurodegenerative model mice using kainic acid, and prolong survival of wild type animal by mimicking caloric restriction. However, oxaloacetate has not been tested in transgenic rodent models of ALS. Thus, we hypothesize that oxaloacetate will prolong survival of ALS model mice by activating mitochondrial biogenesis. I will present a progress report of the project evaluating the effect of systemically administered oxaloacetate for the motor function and lifespan of SOD1G93A transgenic mice. This is a collaboration project between Hiroshi Nishimune and Russell Swerdlow (University of Kansas Medical Center) and A. Baki, Agbas (Kansas City University Medicine and Biosciences). This project has been funded by the Kansas City Area Life Sciences Institute, Neuromusculoskeletal Research Grant.

Speaker: Hiroshi Nishimune, PhD

Hiroshi Nishimune, tenured associate professor of University of Kansas School of Medicine, Department of Anatomy and Cell biology. PhD obtained in Osaka University, Japan. Postdoctoral training performed in France, Dr. Chris Henderson’s lab INSERM U.382 and in USA, Josh Sanes lab at Harvard Univ. Nishimune lab studies organization and degeneration of neuromuscular junctions (the synapse between motor neurons and skeletal muscles) during development, aging, and neuromuscular diseases like ALS. The lab is funded by two NIH R01s and a Kansas City Area Life Sciences Institute, Neuromuculoskeletal research grant.