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Janet Shaw

Professor of Biochemistry

B.A. University of California, Berkeley

Ph.D. University of California, Los Angeles

Research

References

shaw@biochem.utah.edu

Janet Shaw's Lab Page

Janet Shaw's PubMed Literature Search

Research

The Shaw laboratory uses yeast, mammalian cells and mice to study how mitochondrial fission, fusion and movement regulate mitochondrial function and dysfunction in single cells and whole organisms. Our studies are directly relevant to human heath and disease. Defects in mitochondrial membrane dynamics cause embryonic lethality in multicellular organisms and inherited neurological disorders in humans.

In most cells, mitochondria are organized as highly branched tubular networks.  This network is dynamic, undergoing frequent fission and fusion events and moving around on cytoskeletal tracks.  Fission, fusion and transport are regulated by novel GTPases that are conserved from yeast to man.

Mitochondrial Fission:  Mitochondrial fission plays critical roles during development and the cell cycle and is also required for the turnover and degradation of damaged mitochondrial compartments. Our lab identified the first molecular mediator of mitochondrial fission, a dynamin-related GTPase called Dnm1.  Dnm1 forms spirals on the outer mitochondrial membrane that ‘clip’ mitochondrial tubules into smaller pieces.  Two additional molecules, called Fis1 and Mdv1, work together with Dnm1 during the fission reaction. We use a multidisciplinary approach to study how the multi-protein fission complex assembles, constricts and severs the mitochondrial membrane.

Mitochondrial Fusion:  Mitochondrial fusion allows exchange of metabolites, proteins and mtDNA and is critical for optimal mitochondrial function. The Fzo1 GTPase is embedded in the outer mitochondrial membrane and mediates outer membrane fusion.  A second GTPase, Mgm1, mediates inner membrane fusion.  Mutations in the human homologs of Mgm1 and Fzo1 cause inherited neurological diseases including dominant optic atrophy and Charcot-Marie-Tooth Syndrome. We collaborate with researchers at the University of Utah and the National Institutes of Health to identify the molecular basis of these disorders in humans.

Mitochondrial Movement: Mitochondrial movement positions these organelles in all cells and is critical in highly polarized cells such as neurons. Miro proteins are large GTPases on the mitochondrial surface, which bind molecular motors that move mitochondria along cytoskeletal tracks. Mammals have two Miro homologs, Miro1 and Miro2. We have generated Miro knockout mice and are studying the role of Miro proteins in development and neuropathy.

Mitochondrial fusion in human fibroblast cells
Unfused mitochondria are red or green. Fused mitochondria are yellow. Nuclei are blue. (B. Amiott and P. Lott)

References