A research team from Northwestern University have demonstrated that the mitochondria and lysosomes make direct contact with each other in regulating cellular functions. The findings, published today in Nature, provide new insight on organelle dysfunction and has implications in diseases such as Parkinson’s and cancer.
"In this work, we made a new observation that these two organelles are directly talking to each other," said senior study author Dimitri Krainc. "It's a surprising finding that provides new insights into normal cell function and will likely have implications for a number of diseases across the board."
The team employed a myriad of imaging techniques, including electron microscopy, structured illumination microscopy and high spatial and temporal resolution confocal live cell imaging. They identified the formation and regulation of mitochondria–lysosome membrane contact sites, as well as the key protein driving the contact.
The lysosomal protein RAB7 is activated by GTP to promote formation of the contact. Subsequently a protein from the mitochondria is recruited to hydrolyze GTP and release the contact. Elements in lysosomes and mitochondria thus perform a type of bidirectional regulation of each other.
"The discovery of these mitochondria-lysosome contacts is extremely exciting," said first author Yvette Wong. "We now show that these contacts offer a potential site through which mitochondria and lysosomes can crosstalk, and it suggests that defects in the regulation of this contact site may drive the pathogenesis of various human diseases."
Because dysfunction of mitochondria and lysosomes are implicated in neurodegenerative diseases, the team is now following up with investigating how dysfunction of tethering proteins may affect the function of these organelles.
"It's very important that we now know that these organelles are talking to each other directly,” said Krainc. “How exactly these contacts are disrupted in various diseases, including Parkinson's, and how to restore them therapeutically, will be the subject of in-depth investigations in the future."
Image: 3D structure of rat GDP-bound Rab7. Image courtesy of Kirill Alexandrov and RSCB PDB.