Oleh Khalimonchuk, PhD


Oleh Khalimonchuk, PhD
Assistant Professor
N230 Beadle Center
University of Nebraska-Lincoln
Lincoln, NE 68588-0662

(402) 472-8060
Email: okhalimonchuk2@unl.edu



Research Interest

Mitochondria are highly dynamic and complex organelles responsible for cellular energy conversion, a plethora of key metabolic pathways, maintenance of ion homeostasis and programmed cell death. Perturbations of mitochondrial homeostasis and integrity result in dysfunctions that manifest in a spectrum of early to adult-onset neurological and cardiovascular disorders and are contributor to certain types of cancer, type II diabetes and neurodegeneration. Understanding the molecular bases of mitochondrial function/dysfunction is a key for finding ways to combat these currently incurable disorders. Our research utilizes yeast and mammalian cell models to address following questions:

Role of the protein quality control in mitochondrial homeostasis and stress response
Mitochondrial respiration results in the generation of reactive oxygen species (ROS) that may contribute to dysfunction. In addition, reactive intermediates in the biogenesis of the electron transfer chain respiratory complexes can generate ROS. Mitochondrial protein quality control system (MQC) represented by molecular chaperones and proteases is key factors helping cells to cope with homeostatic challenges such as oxidative damage and protein misfolding. MQC contain a number of highly conserved proteases, important functions of which remain obscure. The long-term goal of our research is to deduce why the MQC proteases are essential for mitochondrial homeostasis and their contribution to human mitochondrial disorders. Our data suggest that one MQC protease, Oma1, is required for cells survival under various stress conditions. We seek to understand how Oma1 is activated by cellular stress and why it is important for mitochondrial integrity. Oma1 works in concert with at least two other MQC proteases, iAAA and mAAA, to maintain mitochondrial function. We seek to elucidate the individual roles of various mitochondrial proteases in the preservation of mitochondrial function and how impaired protein turnover leads to a disease.

Biogenesis and maintenance of the protein complexes within the inner mitochondrial membrane
The vast majority of proteins comprising mitochondrial proteome is synthesized in the cytosol and subsequently imported into the organelle, while handful of proteins is derived from mitochondria’s own genome. Inner mitochondrial membrane (IM) is an ultimate destination for a large number of these proteins. Majority of the proteins within the IM are organized into high molecular weight complexes. Some of those complexes, like cytochrome c oxidase, consist of proteins of the dual origin and harbor highly reactive prosthetic groups. To assure normal mitochondrial function, a large number of dedicated chaperones and assembly factors assist and regulate biogenesis and maintenance of mitochondrial protein complexes. We seek to understand how multi-protein complexes within the IM are formed and maintained, and how their erroneous biogenesis due to mutations in assembly factors routs to a disorder.