Optical Control of Mitochondrial Metabolism

­Background

Mitochondria are organelles found in most eukaryotic organisms and they are the powerhouse of the cell. Mitochondria generate an electrochemical proton gradient known as the protonmotive force (PMF). The PMF is like a battery, in that potential energy is stored for eventual release to do work. Mitochondrial dysfunction is implicated in a wide range of diseases and occurs when this organelle fails to produce enough energy for the body to function properly. In the US, mitochondrial diseases are known to annually affect 1 in 5,000 individuals. It is also estimated that 1,000-4,000 children are born with a mitochondrial disease every year, in the same region. Despite major advances in understanding the molecular mechanisms, currently, there are no effective treatments for the disease. The treatment of mitochondrial disorders is mostly performed with different vitamins, co-factors, off-label drugs approved for other indications, and nutritional supplements. Therefore, there is a current need for developing specific therapies for treating mitochondrial diseases.

Technology Overview

Optogenetics uses light-sensitive proteins to control biological functions and when targeted to mitochondria may allow rapid and precise manipulation of the PMF by controlled exposure to light. Researchers at Rochester have developed an optogenetic tool called mitochondria-ON (mtON) due to its ability to mimic the proton pumping activity in response to light, independent of oxygen or substrate availability. In animal models, mtON showed a significant increase in energy production bypassing the requirement for O2 consumption. Additionally, mtON is capable to reverse and control mitochondrial dysfunction and affects whole-animal energy-sensing. mtON’s ability to augment the PMF via optic control opens a new avenue for discovery in metabolic research.

Benefits

mtON represents a novel tool to control mitochondrial function through the use of light and presents an intervention point to treat disease and other negative phenomena. 

Applications

Mitochondrial diseases and diseases where mitochondrial dysfunction is part of the pathology such as diabetes, Alzheimer’s disease and cancer.

URV Reference Number: 6-21020A
Patent Information:
Category(s):
Therapeutic
For Information, Contact:
Matan Rapoport
University of Rochester
585.276.6600
matan.rapoport@rochester.edu
Inventors:
Andrew Wojtovich
Shahaf Peleg
Brandon Berry
Minsoo Kim
Andrea Amitrano
Keywords: