OPA1 in Dominant Optic Athrophy

  • Schwarzenbacher, Robert, (Principal Investigator)

    Project Details

    Description

    A decline in mitochondrial function is well recognized in neurodegenerative diseases and aging, and is thought to play a causal role in their biology.
    Interestingly, mitochondria undergo frequent fission and fusion. This process is regulated by molecular machinery that has been highly conserved during evolution, and includes dynamin-related GTPases, like OPA-1 and Drp-1, that manifest opposing effects. Loss of OPA-1 function, analogous to deficiency of its yeast homologue, Mgm1p, is expected to lead to mitochondrial fission, loss of mitochondrial DNA, respiratory deficits, and an increase in reactive oxygen species (ROS).


    To test this hypothesis and to assist ongoing genetic and cell biological studies in collaboration with Prof. Ella Bossy-Wetzel at The Burnham Institute, LaJolla, CA, we are working on the structural and biophysical characterization of OPA-1, Drp-1 and related proteins.

    The ultimate goal of this project is to identify the molecular mechanism underlying DOA. OPA-1, a dynamin-related GTPase regulating mitochondrial fusion, is mutated in humans with dominant optic atrophy (DOA), leading to degeneration of retinal ganglion cells and childhood blindness.
    Short titleDominant Optic Athrophy
    StatusFinished
    Effective start/end date1/07/06 → 9/06/09

    Fields of Science and Technology Classification 2002

    • 32 Medical Chemistry, Medical Physics, Physiology
    • 3208 Medical biochemistry
    • 3203 Biophysics