Mechanisms directly linking mitochondrial dysfunction to the shortening of telomeres have been discovered, alongside a novel optogenetic technique, which uses light to restore normal function to the mitochondria.
Mitochondrial dysfunction can lead to disease and premature ageing, however the mechanisms involved have not been well understood. Researchers from the University at Buffalo (UB), New York, and collaborators from other institutions, have published two papers explaining the connection between mitochondrial dysfunction and the shortening of telomeres, a key biomarker of premature ageing, and a new optogenetic technique that uses light to control cellular activity, which can be used to study and potentially reverse the interactions that cause mitochondrial diseases and premature ageing.
'Telomeres are specialised DNA sequences that act as caps that stabilise the ends of chromosomes… the shortening of telomeres is generally regarded as an important biomarker of ageing, but for a long time, no one knew the mechanism', commented Professor Taosheng Huang, division chief of genetics at UB's Jacobs School of Medicine and Biomedical Sciences. 'Now we are able to link mitochondrial dysfunction directly to the shortening of telomeres.'
Published in Aging Cell, mouse models were used that carry a genetic defect that accelerates the accumulation of mitochondrial DNA mutations. Single mitochondrial nucleotide changes led to higher levels of reactive oxygen species, increased DNA strand breakage, oxidative damage, shorter average telomere length, and reduced DNA integrity. These events led to premature ageing of the mitochondria.
A further study, co-authored by Professor Huang in Nature Communications described an optogenetic method that used blue light to track and control cellular interactions and induce reversible mitochondrial fission, where mitochondria divide in two. This new method was shown to partially restore the mitochondrial functions of cells that have defects in mitochondrial fission and hence provide a platform for studying mitochondrial fission and treating mitochondrial diseases.
'We describe a technology that we developed that allows us for the first time to directly manipulate the interactions between mitochondria and other organelles in the cell' explained Professor Huang, 'By using optogenetics to force a physical interaction between mitochondria and another cellular component, the lysosome, we were able to restore the mitochondria to a more normal size while also improving their energy production functions'.
The authors believe that these findings could be used as the basis to study, diagnose, and treat mitochondrial disorders.