Cynthia ALSAYYAH- PhD defensis

“Regulation of mitochondrial fusion by the Ubiquitin Proteasome System and physical contacts between mitochondria and peroxisomes in yeast Saccharomyces cerevisiae.” under the direction of Mickael Cohen. 

The 14th september 2021 at 14:30 in IBPC’s Conference room and in visioconference

Mitochondria are highly dynamic organelles that undergo constant fission and fusion of their outer and inner membranes. These processes are critical to maintain essential mitochondrial functions such as oxidative phosphorylation or calcium signaling.

On a molecular basis, mitochondrial fusion and fission both depend on large GTPases of the Dynamin-Related Protein (DRP) family. The DRPs that mediate attachment and fusion of mitochondrial outer membranes are called the Mitofusins. The yeast mitofusin Fzo1 is located in the mitochondrial outer membrane. Its oligomerization promotes mitochondrial tethering followed by mitochondrial outer membrane fusion.

Fzo1 has recently been proposed as a potential tether between peroxisomes and mitochondria when overexpressed. In my thesis, we were able to prove that Fzo1 naturally localizes to peroxisomes and oligomerizes with the mitochondrial Fzo1 thus creating Fzo1-Fzo1 contacts between peroxisomes and mitochondria. We discovered that these Fzo1-mediated contacts allow the mitochondrial transfer of early byproducts of the glyoxylate cycle to stimulate mitochondrial fusion according to cellular fatty acid desaturation levels.