About
Research
Our laboratory is interested in how mitochondria communicate and regulate biological processes at the cellular and organismal level. We currently focus largely on bioactive peptides that are encoded in the mitochondrial genome that mediate mitochondrial regulation to maintain metabolic homeostasis.
Mitochondria are ancient organelles that are thought to have originated from free-living bacteria. They significantly upgraded our ability to extract energy from carbon sources, allowing a more complex system to exist.
Today, mitochondria act as major coordinators of our complex metabolic system. All coordination requires some form of communication, and our lab is interested in how mitochondria have evolved to dynamically communicate to the cell, such that not only did they come to coordinate a complex metabolic system, but also actively regulate metabolic changes during aging and age-related diseases.
Simply put, what were the alphabets of the mitochondrial language that were encoded in the original symbiotic bacterial (proto-mitochondrial) genome, what do they look like today, what are their functions, and how can they help us age better?
Mitochondrial-Encoded Microproteins
As part of their bacterial inheritance, mitochondria have retained an independent genome that is circular (bacterial genomes are still circular). Traditionally 13 protein-coding genes have been annotated in the mitochondrial genome. More recently, we and others have found that the mitochondrial genome also encodes for small/short genes that yield microproteins (gene-encoded microproteins are also actively being unveiled in the nuclear genome).
We have unveiled several functions of mitochondrial-encoded microproteins, largely by leveraging the recently identified MOTS-c (mitochondrial ORF of the twelve S rRNA type c). Some of the topics investigated actively in our lab are:
-Direct nuclear-encoded gene regulation by mitochondrial-encoded microproteins in response to aging-related stress.
-Metabolic and adaptive stress regulation during exercise and aging.
-Immunological origin of mitochondrial-encoded microproteins (i.e. bacterial-derived antimicrobial peptide).
-Role of mitochondrial-encoded microproteins in regulating inflammation and immune cells during aging.
Ultimately, we have 2 genomes, each compartmentalized in the nucleus and mitochondria. We hope to understand how factors encoded in the mitochondrial genome regulate the aging process and age-related diseases. We are continuing to unveil new gene-encoded microproteins in the mitochondrial genome and their biological roles and the underlying mechanisms – stay tuned!
