Quantum tunnelling leads to human disease: genetic blindness in young adults

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Prof. Anastassia Alexandrova

Professor Anastassia Alexandrova and former and current members of her group are part of a UCLA team of researchers using advanced computer tools to examine how molecules interact in the mutated protein that can lead to blindness in young adults.

Alumnus Dr. Jack T. Fuller (Ph.D. ’21, Alexandrova), now a postdoc at Pacific Northwest National Laboratory (PNNL), was the lead author, graduate student Pujan Ajmera co-author, and Alexandrova senior author, on the team’s recent study, published in the prestigious journal the Proceedings of the National Academy of Sciences (PNAS).  Their collaborators, Alfredo Sadun and Steven Barens are from the David Geffen School of Medicine Department of Ophthalmology, and the Doheny Eye Institute.

From UCLA Health Lab Notes:

Leber’s hereditary optic neuropathy is a condition where a specific genetic mutation in the mitochondrial DNA can lead to sudden and permanent blindness in both eyes. This mutation affects the proteins responsible for mitochondrial function in key cells of the retina. However, scientists were uncertain about how this mutation causes impairment in mitochondria, which are like tiny power plants in our cells. Using molecular dynamics simulations, the investigators discovered that this mutation slows down a crucial process called electron transfer to Coenzyme Q10. This slowdown creates conditions that favor the production of harmful substances called reactive oxygen species, which at a threshold leads to cell death by apoptosis. Remarkably, the ROS production is due to enhanced tunnelling and back-propagation of electrons through the implicated protein. The findings help shed light on how the genetic mutation disrupts the functioning of mitochondria, setting off a chain reaction that can eventually lead to blindness.  Read the study published in PNAS.


Penny Jennings, UCLA Department of Chemistry & Biochemistry, penny@chem.ucla.edu.