New research detailing how mitochondria maintain proper function could lead to improved treatments for conditions such as Alzheimer's disease and diabetes.
Mitochondria were found to contain sensors that are involved in the process called mitophagy, whereby damaged or dysfunctional mitochondria are recognised and broken down. These sensors, termed mitoAMPK, are activated under conditions of energetic stress, for example during exercise or fasting.
'Mitochondria are the centre of the universe to me, since literally all cells in our body rely on mitochondria for energy production and must have a bulletproof system to ensure the powerhouses are functioning properly,' said author Professor Zhen Yan from the University of Virginia School of Medicine. 'Chronic diseases such as diabetes, heart failure and Alzheimer's disease that catastrophically impact so many individuals, families and the whole society are caused by problems of the mitochondria in the cells.'
Professor Yan's group established that there are different forms of the mitoAMPK, found in the outer mitochondrial membranes of different cell types. This discovery has advanced broader understanding of mitophagy by demonstrating how mitochondria in precise locations can respond to local environmental cues.
The findings help explain why regular exercise can be beneficial for reducing risk and severity for many chronic diseases and may also be useful in developing new drug treatments or understanding how current drugs work. For example, the authors showed in mouse models that metformin, a common first-line treatment for diabetes, activates mitoAMPK in skeletal muscles only.
'We have developed genetic models for pinpointing the key steps of mitoAMPK activation and are on our way to discover the magic molecules that are controlled by mitoAMPK,' said Professor Yan. 'Society should definitely take advantage of these findings to promote regular exercise for health and disease prevention and develop effective exercise-mimetic drugs.'
Professor Yan and his colleagues will next aim to establish the role of this mitochondrial sensor-based quality control system in other conditions and treatments.
The report was published in the journal Proceedings of the National Academies of Science.