The role of von willebrand domain-containing protein 8 in mitochondrial physiology
Mitobetes project brings a new research on poorly characterized mitochondrial protein involved in important cellular and
physiological processes such diabetes, kidney failure and cancer. It also aims on the role of mitochondria in diabetes, the
disease which affects almost 10% of European population. The mitobetes project has a potential to help to find a new
mitochondrial protein involved in diabetes, find a mechanism of diabetes development, increase the public knowledge about
diabetes and thus helps to decrease EU healthcare costs.
Mitochondria are crucial organelles not only in energy conversion, but also in a plethora of other biological processes. Their
function is closely related to their dynamics, controlled by the pro-fusion proteins Mitofusin (Mfn) 1 and 2 and Optic atrophy 1
(Opa1); and by the fission proteins mitochondrial fission factor (Mff) and dynamin related protein 1 (Drp1). Opa1 not only
controls mitochondrial fusion, but also shape of the mitochondrial cristae, a crucial parameter in determining mitochondrial
function and participation in apoptosis. Opa1 exists in high molecular weight complexes of unknown composition that are
dynamically modulated during cristae remodeling.
Recently, the host laboratory completed a proteomic catalogue of proteins associating with Opa1 in intact cristae and leaving
the complex only when cristae shape was disrupted. Among the hits associating with Opa1, the host lab discovered Von
Willebrand Domain-containing Protein 8 (Vwa8), a mitochondrial protein of unknown function whose higher levels correlate
with worse prognosis of Acute Myeloid Leukemia (AML). Here, I propose to understand the function of Vwa8 in mitochondrial
network and cristae shape, Opa1 function, apoptosis and bioenergetics. This project will not only characterize the role of a
novel protein in involved mitochondrial morphology and function, but also verify if a link between mitochondrial morphology
and AML exists.