Japanese researchers identify protein with potential to prevent aging

Our body is made up of tiny building blocks called cells; inside these cells, there are even smaller parts called organelles. Similar to how our organs, such as the heart or lungs, contribute to our overall health, organelles play crucial roles in ensuring that cells function effectively. For example, mitochondria act as the power sources for the cell, and lysosomes help keep the cells clean.

When these organelles get damaged, it causes problems like , diseases, or disruptions in normal cellular function. HKDC1 to the rescue Scientists at Osaka University found a protein called that helps care for two important organelles: Mitochondria and lysosomes. This protein plays a key role in preventing the cell from aging.

They showed that when the cell is stressed, especially the mitochondria or lysosomes, HKDC1 gets more active. Another protein, known as TFEB, had evidence suggesting its involvement in preserving the function of both organelles. However, no targets of this protein were identified at the time. So, the researchers at Osaka University looked into it and found that TFEB targets a specific gene, HKDC1.

By comparing all the genes of the cell that are active under particular conditions and by using a method called chromatin immunoprecipitation, which can identify the DNA targets of proteins, the team was the first to show that the gene encoding HKDC1 is a direct target of TFEB and that HKDC1 becomes upregulated under conditions of mitochondrial or lysosomal stress.

HKDC1 prevents DNA damage induced cellular senescence To protect mitochondria from damage, there's a process called "mitophagy," which means getting rid of the damaged ones. There are different ways to do this, and one of the well known methods involves proteins named PINK1 and Parkin.

“We observed that HKDC1 co localizes with a protein called TOM20, which is located in the outer membrane of the mitochondria,” lead author Mengying Cui. “And through our experiments, we found that HKDC1, and its interaction with TOM20, are critical for PINK1/Parkin dependent mitophagy.” That takes care of the mitochondrial trash, for lysosomes, which is like a recycling center.

TFEB and HKDC1 also play a crucial role here. “HKDC1 is localized to the mitochondria, right? Well, this turns out to also be critical for the process of lysosomal repair,” explains senior author Shuhei Nakamura. When we reduce HKDC1 in the cell, it messes up the cleanup process within the lysosomes.

This is akin to removing their repairing power, causing the lysosomes to face challenges in self repair when damaged. “You see, lysosomes and mitochondria contact each other via proteins called VDACs. Specifically, HKDC1 is responsible for interacting with the VDACs; this protein is essential for mitochondria–lysosome contact, and thus, lysosomal repair,” added Nakamura.

The multifaceted functionalities of HKDC1, operating prominently within both the lysosomal and mitochondrial domains, serve the dual purpose of averting cellular senescence while concurrently preserving the structural integrity of these vital organelles. Given that malfunctions in these organelles have established associations with the aging processes and the onset of age related diseases, the revelation of HKDC1's pivotal roles presents novel prospects for therapeutic interventions targeting these conditions.

The was published in the journal ..