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The role of Von Willebrand Domain-containing Protein 8 in mitochondrial physiology

Project description

Tracing the link between mitochondrial morphology and acute myeloid leukaemia

Mitochondria are cell energy factories that are involved in the regulation of numerous biological processes. Recently, the host laboratory of the EU-funded Mitobetes project completed a proteomic study of protein associations in intact mitochondria cristae. Among different hits, they identified von Willebrand domain-containing protein 8 (Vwa8), a mitochondrial protein with unknown function whose higher levels correlate with worse prognosis of acute myeloid leukaemia (AML). During the Mitobetes project, the team aims to understand the role of Vwa8 in mitochondrial morphology and function. The objective is to find a link between mitochondrial morphology and AML. In addition, Mitobetes will study if this poorly characterised mitochondrial protein is involved in pathological processes associated with kidney failure and diabetes.

Objective

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.

Coordinator

UNIVERSITA DEGLI STUDI DI PADOVA
Net EU contribution
€ 183 473,28
Address
Via 8 febbraio 2
35122 Padova
Italy

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Region
Nord-Est Veneto Padova
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00