UC study reshapes understanding of interaction between organelles in animal cells

The research, led by UC’s Jiajie Diao, PhD, was published online March 15 in the journal Cell Reports.

The study focused on the lysosome, an organelle within animal cells that contributes to a number of cellular functions. This includes helping to break down materials into more useful energy sources, similar to how the intestines digest food into usable nutrients on the whole-body level.

To accomplish these digestive functions, lysosomes need an acidic pH environment to help break down cellular materials, and to achieve this acidity, they need to import free protons from other parts of the cell.

Traditionally, it was thought that lysosomes only gather these extra protons from the cytosol, the intracellular fluid that surrounds organelles. But using a newly synthesized mitochondrial polarity probe, Diao and team found mitochondria are major proton donors to lysosomes, helping accomplish lysosomal acidification.

“Acidification is the most important step for lysosomal functions. We completely changed people's minds on the source of protons for acidification,” said Diao, associate professor in the Department of Cancer Biology in UC’s College of Medicine. “For my 25 years of research until now, this paper may be the only one that can be included in future textbooks.”

Using a first-in-class lysosome content digestion probe, they additionally found lysosome content degradation increases at sites of mitochondria-lysosome contact (MLC). MLC is a newly discovered connection within cells that has not been researched thoroughly, Diao noted.

“Furthermore, physically bringing mitochondria and lysosomes together can trigger lysosomal acidification at MLCs,” Diao said. “Overall, these findings substantially reshape our understanding of the mechanisms underpinning lysosomal acidification and reveal another non-ATP-synthesis function of the proton gradient.”

Next, the team will focus on diseases caused by defective MLC and potential treatments that target MLC.

Diao and his colleagues published research in 2022 that found enhancing MLC can help mitochondrial function, but there are not many other known attempts to leverage this contact point as a treatment.

Featured image at top: Jiajie Diao works in his lab. Photo/Colleen Kelley/UC Marketing + Brand