By comparing all the genes of the cell that are active under particular conditions, and by utilizing a technique called chromatin immunoprecipitation, which can identify the DNA targets of proteins, the group was the very 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.Overview: Both mitochondrial and lysosomal tension promote TFEB nuclear translocation, followed by increased HKDC1 expression.” We observed that HKDC1 co-localizes with a protein called TOM20, which is situated in the outer membrane of the mitochondria,” explains lead author Mengying Cui, “and through our experiments, we discovered that HKDC1, and its interaction with TOM20, are critical for PINK1/Parkin-dependent mitophagy. Minimizing HKDC1 in the cell was revealed to interfere with lysosomal repair work, showing that HKDC1 and TFEB assistance lysosomes to recuperate from damage.
By comparing all the genes of the cell that are active under particular conditions, and by utilizing a technique called chromatin immunoprecipitation, which can determine the DNA targets of proteins, the group was the first to reveal that the gene encoding HKDC1 is a direct target of TFEB, and that HKDC1 ends up being upregulated under conditions of lysosomal or mitochondrial stress.Overview: Both mitochondrial and lysosomal stress promote TFEB nuclear translocation, followed by increased HKDC1 expression.” We observed that HKDC1 co-localizes with a protein called TOM20, which is situated in the external membrane of the mitochondria,” discusses lead author Mengying Cui, “and through our experiments, we found that HKDC1, and its interaction with TOM20, are vital for PINK1/Parkin-dependent mitophagy.” Role of HKDC1 in Lysosomal RepairSo, put simply, HKDC1 is brought in by TFEB to assist take out the mitochondrial garbage. Reducing HKDC1 in the cell was revealed to interfere with lysosomal repair work, suggesting that HKDC1 and TFEB assistance lysosomes to recuperate from damage.