Mitochondria are cytoplasmic organelles, critical to basic cellular function due to their principal role in energy production and mitochondrial dysfunction is implicated in the etiology of many human diseases. They contain their own genome (mtDNA) that is transmitted maternally. Current dogma holds that mammalian cells transmit their nuclear and mitochondrial genomes exclusively vertically to daughter cells, during cell divisions. However, and rather unexpectedly, our preliminary studies have demonstrated horizontal exchange of mitochondria and mtDNA between cells that are not in a parent-offspring relationship. The objective of this proposal is to test our main hypothesis that horizontal mtDNA transfer is common during normal development and is critical to maintain or rescue the metabolic potential of cells. Our team seeks to uncover genetic, epigenetic and cellular mechanisms governing horizontal mtDNA acquisition and find answers on how, when and why cells within a body donate and accept mtDNA. The ultimate goal is to understand mtDNA stability in high energy-demanding organs and tissues, particularly during aging. Our research will likely have a significant impact on our understanding of mtDNA biology and guide the development of future therapeutic approaches to maintain mitochondrial genome integrity by experimental mitochondrial transfer and replacement.

Public Health Relevance

This project will address fundamental questions concerning biology of the mitochondrial genome during aging. When completed, we will provide clear evidence as to whether or not different cells within a body donate and accept mitochondria from each other.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG062459-02
Application #
9902293
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Fridell, Yih-Woei
Project Start
2019-04-01
Project End
2024-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239