Thread by @DrAnneCarpenter

15 years in the making, we confirmed that mitochondria -the powerhouse of the cell- have an unusual localization in patients who experience psychosis (including schizophrenia and bipolar disorders). You’ll never guess what kind of patient cells we used to make this discovery...🧵

… unless you’ve heard me talk about it, which I’ve done a lot over the past decade :D

Including in this Quanta video:

The answer is skin cells. Skin cells! That seems really odd, but lots of cells share lots of components and processes that are used in different ways in different cell types. And not-fun fact: psychotic symptoms are associated with skin abnormalities.

This mislocalization, in which mitochondria cluster too close to the nucleus in the middle of cells, may deprive cells, including brain cells, of energy and metabolites needed for growth, function, and repair.

We then queried cell image databases to find chemicals and genetic perturbations that change mitochondrial localization in either direction, towards or away from the nucleus. Many have known involvement in mental function!

This means that we can screen for potential novel drugs for schizophrenia and bipolar disorder in easily-grown skin cells, using mitochondria as a simple readout. In fact, a team at NIH’s NCATS is working on this now! Stay tuned.

Congrats to the project team across McLean Hospital & Broad Institute! First authors: Marzieh Haghighi & Donna McPhie! Co-senior author Bruce Cohen. Team: Mohammad Rohban, Erin Weisbart, David Logan, Kyle Karhohs, Jessica Ewald, Johan Fredin Haslum, Beth Cimini, Shantanu Singh.

Thanks to the funders who believed in us, enabling us to complete this work in pieces over time: NIH NIGMS, Merkin Institute, BroadIgnite, BBRF, Harvard-MIT Neurodiscovery program, and the Program for Neuropsychiatric Research at McLean Hospital.

Pre-print here:
biorxiv.org/content/10.110…