Nat Aging: Fantastic! Genetically modified mitochondria can be charged with light energy and extend nematode lifespan

A new study draws lessons from the renewable energy sector and shows that genetically modified mitochondria can convert light energy into chemical energy that cells can use, ultimately extending the lifespan
of Caenorhabditis elegans.
While the prospect of using sunlight to recharge cells in humans is more science fiction than science, the findings shed light on important mechanisms
in the aging process.
The findings were published online Dec.
30, 2022 in the journal Nature Aging, in the paper "Optogenetic rejuvenation of mitochondrial membrane potential extends C.
elegans lifespan.
"

Dr.
Andrew Wojtovich, co-corresponding author and associate professor of anesthesiology and perioperative medicine at the University of Rochester Medical Center, USA, said, "We know that mitochondrial dysfunction is a consequence of
aging.
The new study found that simply using light-powered mitochondria to boost metabolism could lead to longer, healthier life for laboratory nematodes
.
These findings and new research tools will allow us to further study mitochondria and identify new ways
to treat age-related diseases and age healthier.
”

Mitochondria are organelles
found in most cells of the human body.
Often referred to as cellular energy factories, mitochondria use glucose to produce adenosine triphosphate (ATP), a compound that powers key functions in cells, such as muscle contractions and electrical impulses
that help nerve cells communicate with each other.

ATP production is the result of reactions that are achieved by the exchange of protons on the membrane that separates the different compartments of mitochondria, and the efficiency of this reaction is called membrane potential
.
Membrane potential, which is known to decline with age, is a topic of great interest to the scientific community because of its potential role
in some age-related diseases, such as neurodegenerative diseases.

The new study involves Caenorhabditis elegans, a tiny nematode that, like fruit flies, has long been a research tool used by scientists to understand basic biological principles that, in many cases, apply to the entire animal kingdom
.

To carry out these experiments, researchers from the University of Rochester in the United States, the German Institute for Farm Animal Biology and the Technical University of Munich turned to optogenetics, a research tool
that uses light to control biological processes within cells.
Neuroscientists use optogenetics to target and activate specific neurons to study patterns of brain activity
.
This tool allowed them to target and manipulate the activity of the C.
elegans mitochondria--- a task made easier
because the worm is transparent.

mtON increases the membrane potential
of mitochondria in vivo.
Image from Nature Aging, 2022, doi:10.
1038/s43587-022-00340-7
.

The authors genetically engineered the mitochondria of C.
elegans so that they contained a light-activated proton pump obtained from the fungus, an achievement they first described in a paper in the journal EMBO Reports in 2020 (EMBO Reports, 2020, doi:10.
15252/embr.
201949113).

In the new study, when exposed to light, this proton pump moves charged ions across the mitochondrial membrane, using the energy of the light to charge
the mitochondria.
This process, which they call mitochondria-ON (mtON), increases membrane potential and ATP production, and increases the lifespan of nematodes by 30%~40%.

Lead author Dr Brandon Berry, who received his PhD in physiology from the University of Rochester, said, "Mitochondria are similar to industrial power plants in that they burn a carbon source, mainly glucose, to produce useful energy
for cells.
What we're basically doing is connecting solar panels to existing power plant infrastructure
.
In this study, solar panels are the optogenetic tool mtON.

Subsequently, in addition to the normal combustion pathway, normal mitochondrial mechanisms are able to use light energy to provide ATP
.
”

This new study is important because it provides new insights into the complex biological role mitochondria play in the human body, a topic
that the scientific community is only now beginning to understand.
The study has also developed a new method to manipulate and study mitochondria
in the environment of living cells.
This can serve as an important platform
to study mitochondria and identify ways to intervene and support function.

Berry said, "We need to know more about how mitochondria really behave
in animals.
First in nematodes, as in this new study, but then in human cell cultures and rodents
.
In this way, future studies will provide some information in order to target the most likely participants
in human disease and aging.
(Biovalley Bioon.
com)

Resources:

1.
Brandon J.
Berry et al.
 Optogenetic rejuvenation of mitochondrial membrane potential extends C.
elegans lifespan.
Nature Aging, 2022, doi:10.
1038/s43587-022-00340-7.

2.
Solar Panels for Cells: Light-Activated Proton Pumps Generate Cellular Energy, Extend Life