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Access Type
WSU Access
Date of Award
1-1-2025
Degree Type
Thesis
Degree Name
M.S.
Department
Molecular Biology and Genetics
First Advisor
Siddhesh Aras
Abstract
Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) is a bi-organellar protein localized to the mitochondria and nucleus. In mitochondria, MNRR1 supports oxidative phosphorylation (OxPhos) and inhibits intrinsic apoptosis, while in the nucleus, it regulates the transcription of ~5000 genes, including many linked to cancer. MNRR1 is frequently upregulated in cancers. Using triple-negative breast cancer (TNBC) as a model, we aim to define MNRR1’s anti-apoptotic mechanism. Intrinsic apoptosis is triggered by an imbalance between pro- and anti-apoptotic proteins, leading to cytochrome c release from the outer mitochondrial membrane (OMM). MNRR1 knockout or inhibition sensitizes cells to apoptosis. We show that non-phosphorylated mitochondrial MNRR1 binds VDAC, an OMM protein, via its mitochondrial localization sequence (MLS), enhancing VDAC–Bcl–XL interaction to block cytochrome c release. We hypothesize that MNRR1 threonine phosphorylation activates its anti-apoptotic function. Our findings suggest MNRR1 is a potential therapeutic target in TNBC, warranting further validation in additional TNBC models.
Recommended Citation
Elshenawy, Habiba Ihab Ahmed, "Characterizing The Role Of Mitochondrial Nuclear Retrograde Regulator 1 (mnrr1) As An Anti-Apoptotic Agent In Triple-Negative Breast Cancer (tnbc)" (2025). Wayne State University Theses. 1005.
https://digitalcommons.wayne.edu/oa_theses/1005