This protein keeps your cells young

This protein keeps your cells young

The protein, called HKDC1, plays an important role in combating cell aging. Thus, this discovery may open new horizons for research into aging and age-related diseases.

As you get older, you can notice this in all kinds of ways. Back pain when waking up, double vision, or feeling tired more quickly. During this “deterioration” – as it is often optimistically expressed – your body slowly becomes more fragile. As a result, everything starts to work a little less well, you become more vulnerable, and eventually, if all goes well, you die of “senescence”: a collective term for the aging of all your cells.

However, some cells in our bodies age faster than others. Consider the liver of a person who drinks a lot of alcohol, or the lungs if a person smokes a lot. But also due to diseases, genetics or other forms of wear and tear, our body as a whole does not become so fragile so quickly. So it is interesting for scientists to see what exactly causes cell aging, and whether we can do something about it. This also applies to researchers from Osaka University. In their research, they looked at the interactions between organelles, which are the organs of the cell. There they discovered a protein called HKDC1, which maintains the health of two of those organelles: mitochondria and lysosomes.

Mitochondria and lysosomes
Mitochondria are the power plants of the cell. One of its functions is to produce energy so that the body can function properly. This energy comes from the food we eat, which is broken down into substances that cells can use. In the case of mitochondria, for example, sugars are broken down into fuel glucose, which the mitochondria then use to produce energy. With this sorting and exchange of nutrients, there is always something left that the cells can no longer use. This is cleaned up by lysosomes: the cell's garbage collectors.

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These are large-scale processes that happen at breakneck speed throughout the day in all those 37 trillion cells that make up your body. So it's not surprising that every now and then a part gets damaged or starts working less well. But the result is that the cell may age or become diseased. This can also have consequences for the entire body. It's possible to miss a single cell, but the more often it happens, the faster you'll get tired, less able to think straight, or get sick.

Both mitochondrial and lysosomal stress induce nuclear translocation of TFEB, followed by increased HKDC1 expression. HKDC1 stabilizes PINK1 through interaction with TOM70, facilitating PINK1/Parkin-dependent mitophagy. Moreover, the HKDC1 and VDAC proteins with which it interacts are important for repairing damaged lysosomes and maintaining communication between mitochondria and lysosome. HKDC1 prevents DNA damage-induced cellular senescence by maintaining mitochondrial and lysosomal homeostasis – 2024 Cui et al.

Replace the broken lamp
The protein HKDC1 seems to help greatly prevent this. The protein works with another protein called TFEB, which is a type of coordinator in the cell. When mitochondria or lysosomes are under stress, TFEB tells the cell to produce more HKDC1. HKDC1 then translocates to mitochondria and lysosomes and performs maintenance there. For example, it gets rid of damaged mitochondria to make room for new, healthy mitochondria (mitophage). If lysosomes are damaged, HKDC1 helps repair them by contacting mitochondria through other proteins (lysosomal repair). It's as if the HKDC1 spends all day replacing broken light bulbs and patching flat tires.

Interaction via proteins
It is able to do this so well because of where the researchers found the protein. “HKDC1 is located in the mitochondria,” says researcher Shuhei Nakamura. “This appears to be critical for the lysosomal repair process. In this process, lysosomes and mitochondria must communicate with each other via specific proteins. Proteins that HKDC1 specifically interacts with.” The protein can easily regulate this from the location of HKDC1 in mitochondria. The researchers were also able to prove this in their study by reducing HKDC1 in the cell, which suddenly disrupted the recovery of lysosomes.

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Researchers say these two different functions of HKDC1 help prevent cell aging. According to them, this discovery could open new horizons for new research into aging and age-related diseases such as osteoporosis or Parkinson's disease. But before that, they first want to further investigate exactly how HKDC1 works.

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