Objective
Autosomal dominant optic atrophy (ADOA) is caused by mutations in Optic Atrophy 1 (OPA1), a dynamin-related protein of the inner mitochondrial membrane. During the last years, we clarified that OPA1 is a multifunctional protein participating in genetically distinct pathways of mitochondrial fusion and cristae remodelling, both impaired by pathogenetic mutations. We extended our investigation on the (dys)function of OPA1 and our preliminary results indicate that (i) OPA1 is a key modulator of apoptosis and autophagy in vivo; (ii) OPA1 is a master regulator of mitochondrial cristae architecture, impacting on respiratory chain supercomplex assembly and mitochondrial metabolism; (iii) increased autophagy in axons of retinal ganglion cells carrying pathogenic OPA1 depletes them of mitochondria; (iv) OPA1 resides in multimolecular complexes that comprise potential keyregulators of its multiple functions. We therefore hypothesize that by engaging in interactions with different partners, OPA1 regulates mitochondrial functions. Its mutations increase autophagy and susceptibility to apoptosis, especially in RGCs. These multiple regulatory points offer several potential targets for therapeutic strategies that can interfere with the natural course of the disease. In order to verify our hypothesis, we plan to address: (i) how OPA1 regulates mitochondrial metabolism from the cristae; (ii) how changes in OPA1 levels and function impinge on autophagy, especially in RGC; (iii) if the changes in mitochondrial metabolism and autophagy can be exploited therapeutically in vitro and in vivo. This integrated approach aims at unraveling the pathogenesis of ADOA, and therefore to pave the way for its treatment. At the same time, we expect to clarify how mitochondria participate in key cellular metabolic and quality control processes.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-CIG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
35122 PADOVA
Italy
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