OPA1 in Dominant Optic Athrophy

  • Schwarzenbacher, Robert, (Projektleitung)



    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.
    KurztitelDominant Optic Athrophy
    Tatsächlicher Beginn/ -es Ende1/07/069/06/09

    Systematik der Wissenschaftszweige 2002

    • 32 Medizinische Chemie, Medizinische Physik, Physiologie
    • 3208 Medizinische Biochemie
    • 3203 Biophysik