NRI study: Insufficient energy production by mitochondria can lead to neural degeneration

Mitochondria are the powerhouses of human cells. They convert the energy of food molecules into chemical energy in the form of adenosine triphosphate (ATP) that our cells need to function normally and communicate with other cells in the body.

In a fascinating study recently published in PLOS Biology, Dr. Hugo Bellen, Manish Jaiswal and their colleagues at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s found that insufficient energy production by the mitochondria can cause photoreceptor neurons in the retina to degenerate.

Mitochondrial dysfunction is associated with a number of metabolic and neurological diseases such as Leigh’s syndrome, progressive optic neuropathy and progressive blindness. Previous studies suggest that increased oxidative stress – state of cellular imbalance that damages a number of biomolecules such as lipids, proteins and DNA – can lead to mitochondrial dysfunction which can cause neural degeneration. But, the authors of this study say this may not always be the case every time.

In an unbiased genetic screen, Bellen and his team found that mutations in three different genes that regulate mitochondrial ATP production caused light-dependent degeneration of photoreceptor neurons in the eyes of fruit flies independent of oxidative stress.

Defects in human homologs of each of the genes cause disease. Loss of the LRPPRC gene is implicated in Leigh’s syndrome, an autosomal recessive neurodegenerative disorder, while mutations in pyruvate dehydrogenase are linked to pyruvate dehydrogenase E1-alpha deficiency. Finally, the loss of citrate synthase results in tumor malignancies.

“Our study shows that pathological conditions that arise due to mitochondrial dysfunction cannot always be attributed to excessive oxidative stress,” Bellen said. “Some mitochondrial diseases may be a secondary result of insufficient energy production. It is important to investigate cellular mechanisms besides oxidative stress in mitochondrial associated diseases.”

To read more about their study, click here. To read their article in PLOS Biology, click here.