Northwestern Medicine scientists discovered for the first time that mitochondria and lysosomes are in direct contact to regulate their respective functions. These findings were published in Nature.
“In some ways, we assume that scientists have discovered all the major inner workings of our cells in the 21st century. And yet in this work, we made a new observation that these two organelles are directly talking to each other,” said principal investigator Dimitri Krainc, MD, Ph.D., the Aaron Montgomery Ward Professor and chair of The Ken and Ruth Davee Department of Neurology. “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.”
Every cell of the body is dependent on mitochondria and lysosomes. Lysosomes can recycle waste material, while mitochondria provide energy. Many diseases have been linked to the dysfunction of these organelles, including cancer and neurodegenerative disorders.
In previous studies published in Science, Krainc’s lab had identified a functional link between mitochondrial dysfunction and lysosomal dysfunction during Parkinson’s disease. However, this study is the first to establish direct physical contact between these two organelles.
The scientists used video microscopy to observe the formation of stable contacts within living cells by using fluorescent tagging. Other advanced imaging techniques were also used by the authors, including electron microscopy, super-resolution imaging, and electron microscopy, to reveal that RAB7, a lysosomal protein, regulates the formation and subsequent loosening of these contacts.
“The discovery of these mitochondria-lysosome contacts is extremely exciting,” said first author Yvette Wong, Ph.D., a postdoctoral fellow in Krainc’s laboratory. “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.”
Scientists are currently investigating whether the dysfunction of the proteins that tether mitochondria to lysosomes may impact the function of organelles. This is because some mutations in these proteins have been linked to neurological disorders.
“It’s very important that we now know that these organelles are talking to each other directly. 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,” said Krainc, also director of the Center for Neurogenetics, a professor of Neurological Surgery and Physiology at Feinberg, and a professor of Neurobiology at the Weinberg College of Arts and Sciences.
Daniel Ysselstein, Ph.D., a postdoctoral fellow in Krainc’s laboratory, was also a co-author of the paper.