Restricted Research - Award List, Note/Discussion Page

Fiscal Year: 2021

320  The University of Texas Rio Grande Valley  (84616)

Principal Investigator: Gilkerson, Robert

Total Amount of Contract, Award, or Gift (Annual before 2011): $ 435,900

Exceeds $250,000 (Is it flagged?): Yes

Start and End Dates: 7/1/20 - 6/30/24

Restricted Research: YES

Academic Discipline: N/A

Department, Center, School, or Institute: Biology

Title of Contract, Award, or Gift: Interaction of mitochondrial fusion and transmembrane potential in diabetic cardiovascular damage

Name of Granting or Contracting Agency/Entity: National Institutes of Health (NIH)

Program Title: Support of Competitive Research (SCORE) Research Continuance Award (SC3 Clinical Trial Not Allowed)
CFDA Linked: Biomedical Research and Research Training


This proposal explores the regulation of optic atrophy-1 (OPA1) as a mediator of mitochondrial fusion in mammalian cells. To maintain bioenergetic homeostasis and prevent apoptosis, mitochondria balance their organization between a united, reticular network (OPA1-mediated fusion) and a fragmented population of individual organelles (DRP1-mediated fission). The transmembrane potential across the mitochondrial inner membrane (∆ψm) is required for mitochondrial fusion, linking organellar function and structural dynamics: when mitochondria maintain an intact ∆ψm, OPA1 carries out inner membrane fusion and mitochondrial interconnection. If ∆ψm is lost, OPA1 is cleaved, causing fragmentation of the mitochondrial network and promoting apoptotic cell death. While the OMA1 protease is known to cleave OPA1 in response to loss of ∆ψm, the mechanistic and developmental regulation of this process is unclear. Our prior studies have demonstrated that retinoic acid (RA) causes induction of ∆ψm-sensitive OPA1 cleavage in a robust developmental switch, and OMA1 mediates a sharply-defined threshold of ∆ψm required for mitochondrial fusion. These insights motivate our aims: 1) to explore how RA-mediated differentiation activates OPA1 cleavage in mammalian cells, and 2) how modulation of OMA1/OPA1 balance impacts mitochondrial fusion/fission balance. This research has the potential to provide key mechanistic understanding of a crucial mitochondrial role in cellular homeostasis, with relevance to a wide range of human pathologies. SAMs 1.1.1

Discussion: No discussion notes


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