HKDC1 protein found crucial to maintaining two mitochondria subcellular structures, mitochondria and lysosomes

Just as healthy organs are vital to our well-being, healthy organelles are vital to the proper functioning of the cell. These subcellular structures carry out specific jobs within the cell; for example, mitochondria power the cell, and lysosomes keep the cell tidy.

Although damage to these two organelles has been linked to aging, cellular senescence, and many diseases, the regulation and maintenance of these organelles have remained poorly understood. Now, researchers at Osaka University have identified a protein, HKDC1, that plays a key role in maintaining these two organelles, thereby acting to prevent cellular aging.

There was evidence that a protein called TFEB is involved in maintaining the function of both organelles, but no targets of this protein were known. 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.

One way that mitochondria are protected from damage is through the process of "mitophagy", the controlled removal of damaged mitochondria. There are various mitophagy pathways, and the most well-characterized of these depends on proteins called PINK1 and Parkin.

"We observed that HKDC1 co-localizes with a protein called TOM20, which is located in the outer membrane of the mitochondria," explains lead author Mengying Cui, "and through our experiments, we found that HKDC1, and its interaction with TOM20, are critical for PINK1/Parkin-dependent mitophagy."