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Humboldt-Universität zu Berlin - IRI Life Sciences

Humboldt-Universität zu Berlin | IRI Life Sciences | Scientific Events | IRI Talks | Dates | IRI-Talk - Lynae Brayboy: "Dysfunctional MDR-1 disrupts mitochondrial homeostasis"

IRI-Talk - Lynae Brayboy: "Dysfunctional MDR-1 disrupts mitochondrial homeostasis"

When Dec 06, 2019 from 04:00 PM to 05:00 PM (Europe/Vienna / UTC100) iCal
Where IRI Life Sciences, Philippstr. 13, Building 18, 3rd Floor, Room 410

Talk Chrismas

 

 

 

 

 

 

 

Abstract

Dysfunctional MDR-1 disrupts mitochondrial homeostasis in the oocyte and ovary

Multidrug resistance transporters (MDRs) are best known for their pathological role in neoplastic evasion of chemotherapeutics and bacterial antibiotic resistance. However, MDR-1 is expressed abundantly in the ovary. Our group has found that MDR-1 is present in the oocyte mitochondrial membrane, and it protects the female gamete from oxidative stress. This is significant since the oocyte has more mitochondria than any other cell in the body and the oocyte contributes all of the mitochondria for the developing embryo. Female Mdr1a mutant mice have no significant difference in ovarian follicular counts and stages, nor in reproductively functioning hormone levels, yet these mice are significantly more vulnerable to gonadotoxic chemotherapy. The immature germinal vesicle oocytes have chronically elevated reactive oxygen species and have abnormal mitochondrial membrane potential. The Mdr1a mutant ovaries have a dramatically different transcriptome profile with upregulation of genes involved in metabolism. The mutant ovaries have a significant over-accumulation of metabolites involved in the tricarboxylic acid cycle (TCA). Our findings indicate that functionality of MDR-1 reveals a critical intersection of metabolite regulation, oxidative stress, and mitochondrial dysfunction that has direct implications for female infertility due to poor quality oocytes, premature reproductive aging due to oxidative stress, and gonadoprotection.