Funded Research

The Role of Cell-to-Cell Transfer of Mitochondria in Regulation of Metabolism and Obesity
Principal Investigator(s):
  • Jonathan Brestoff, M.D., Ph.D., M.P.H Pathology and Immunology
Status:
Completed
Center(s):
  • Center for Metabolism and Immunity
Award Mechanism:
Postdoctoral Fellowship
Project Period:
2/1/2019 - 1/31/2021
Total Amount:
$60,000

Project Summary

Obesity affects 16% of children and adolescents.  Consequently, there is an urgent need to better understand the factors that regulate that disease.  Recent studies indicate that immune cells such as macrophages contribute to the development of obesity and associate metabolic dysfunction.  However, how the immune system regulates the development of obesity remains poorly understood.  In preliminary studies, I found for the first time that adipocytes transfer their mitochondria to macrophages in fat.  This process is impaired in obesity, suggesting that mitochondria transfer is physiologically important.  Additionally, a genome-wide CRISPR-knockout screen identified Exostosis 1 (Ext1) as potentially required for mitochondria transfer.  Collectively, these data provoke the hypothesis that intercellular mitochondria transfer is a previously unrecognized mechanism that regulates macrophage function and the development of obesity.

Specific aims

·         We will investigate whether intercellular mitochondria transfer affects the function of recipient macrophages to limit obesity.

·         We will test whether expression of Ext1 by macrophages is required for intercellular mitochondrial transfer and limiting the development of obesity in young or adult mice.

Potential impact on child health

This work may have broad scientific implications for a variety of diseases involving mitochondrial dysfunction, including pediatric obesity, and may lead to the discovery of new therapeutic strategies and targets.