Maintaining healthy organelles within cells is just as crucial as having healthy organs for overall well-being. Organelles, these tiny structures inside cells, perform specific tasks; for instance, mitochondria power the cell, while lysosomes handle cellular cleanliness.
Researchers at Osaka University have unveiled the significance of a protein called HKDC1 in preserving these critical organelles, contributing to staving off cellular aging. Prior to this discovery, understanding how these structures are regulated and sustained remained quite murky.
They found that TFEB, a protein previously associated with maintaining organelle function, directly targets the gene responsible for HKDC1. Under conditions of stress affecting mitochondria or lysosomes, HKDC1’s activity gets ramped up, indicating its pivotal role in the upkeep of these organelles.
HKDC1’s involvement in preserving mitochondria involves a process termed “mitophagy,” which rids the cell of damaged mitochondria. Crucially, HKDC1’s interaction with TOM20, a protein within the mitochondrial outer membrane, was observed as critical for a specific type of mitophagy dependent on PINK1/Parkin proteins.
Essentially, HKDC1, directed by TFEB, aids in mitochondrial cleanup. But its relevance isn’t just limited to mitochondria; it extends to lysosomes as well. Diminishing HKDC1 in the cell was found to disrupt lysosomal repair, underscoring its collaboration with TFEB in aiding lysosomes to recover from harm.
Interestingly, HKDC1’s presence at mitochondria is essential not only for mitochondrial function but also for lysosomal repair. Its interaction with VDACs, proteins linking lysosomes and mitochondria, plays a pivotal role in facilitating contact between these organelles, crucial for proper lysosomal function.
This dual role of HKDC1, pivotal in both lysosomes and mitochondria, serves to maintain cellular health, thus potentially averting cellular aging and related conditions. Understanding these mechanisms could pave new paths for therapeutic interventions in age-related diseases linked to organelle dysfunction.