Mitochondrial membrane permeability crucial to metabolism and ageing

The lifespan of genetically-modified roundworms can be extended by using light to power their mitochondria, a new study has revealed.

Mitochondria are the organelles responsible for producing adenosine triphosphate (ATP) from glucose, needed for muscle contraction and immune signalling; however, as they age, their function decreases, as characterised by lower voltage potentials across their inner membranes. A light-powered proton pump was inserted into roundworms' (C. elegans) mitochondria inner membrane to increase their voltage potentials and when illuminated, the pump facilitated the transfer of protons across the membrane, referred to as the 'mitochondria on' (mtON) tool.

'We know that mitochondrial dysfunction is a consequence of ageing… This study found that simply boosting metabolism using light-powered mitochondria gave laboratory worms longer, healthier lives. These findings and new research tools will enable us to further study mitochondria and identify new ways to treat age-related diseases and age healthier' said Professor Andrew Wojtovich, senior author of the study and associate professor at the University of Rochester, New York.

The mtON tool maintained the mitochondria's function as they aged and extended their lifetimes by 30-40 percent. The increased efficiency of the illuminated genetically-modified roundworm's mitochondria was also demonstrated by their greater thrashing (lateral movement) when in liquids, a key demonstration of increased ATP production.

The study, published in Nature Ageing, selected roundworms because they are optically transparent, meaning their cells can be observed under a microscope and thus, it is easier to specify which sections of the roundworms are illuminated. They are also simpler creatures than humans, but still possess mitochondria that perform the same functions. Further, their short lifespans of two to three weeks make it simpler to measure any increased longevity.

'Mitochondria are similar to industrial power plants in that they combust a source of carbon, primarily glucose, to produce useful energy for the cell… What we have done is essentially hooked up a solar panel to the existing power plant infrastructure. In this instance, the solar panel is the optogenetic tool mtON. The normal mitochondrial machinery is then able to harness the light energy to provide the ATP in addition to the normal combustion pathway.' said Dr Brandon Berry, the study's first author and researcher at the University of Washington.

The ageing of mitochondria and their decreased functioning are thought to be linked to many neurodegenerative diseases, such as Alzheimer's. Following on from this work, there are many questions as to how a mitochondrion's membrane voltage potential influences other redox species including NAD+ and NADH which are key in ATP production in mitochondria. By better understanding the mechanisms by which mitochondria age in species like roundworms, the role of mitochondria in age-related diseases in humans may be better treated.