The powerhouse of cells is the mitochondria, an engine that relies on proteins to drive the cell’s work.
In the past few decades, scientists have been studying proteins in these metabolic epicenters, and have linked these proteins to more than 150 distinct human disorders — often in rare or poorly understood diseases.
And yet still hundreds of other mitochondrial proteins lack clear functions and some 40% of mitochondrial disorders remain unresolved.
Now, researchers at the Morgridge Institute for Research and Washington University School of Medicine in St. Louis have analyzed dozens of mitochondrial proteins of unknown function and suggested functions for many of them.
The findings, published May 25, 2022, in Nature, indicate that understanding how mitochondria’s hundreds of proteins work together to generate power and perform the organelles’ other functions could be a promising path to finding better ways to diagnose and treat poorly understood conditions.
The collaboration started in 2016 when David Pagliarini, a Morgridge affiliate now at Washington University School of Medicine, and Joshua Coon, the Thomas & Margaret Pyle Chair at the Morgridge Institute and a professor of biomolecular chemistry at the University of Wisconsin-Madison, teamed up.
The project was kickstarted with the support of a UW 2020 grant and was further supported by a joint NIH P41 Center grant.
The Coon Lab provided the technical tour de force to dig deep — deeper than anyone else at the time — to survey 203 CRISPR-mediated HAP1 cell knockout lines and characterize the unknown function of over 50 mitochondrial orphan proteins.