What is disease? Our bodies have evolved elaborate mechanisms to maintain molecular, cellular, and organismal processes within a physiologically “normal” range, even in the face of perpetual changes (e.g. aging, diet, etc). A state of disease can be said to ensue when the ability to maintain this homeostasis is compromised. Consequently, understanding how homeostasis is achieved, and how it is compromised, can provide key insights into how diseases unfold. The Patel Lab takes a basic science approach to study mitochondrial homeostasis.

 

Mitochondria schematic pdf

Mitochondria lie at the heart of cellular metabolism and energy production. Mitochondrial dysfunction is known to afflict every organ in the human body and has been implicated in numerous diseases including inborn errors of metabolism, brain encephalopathies, muscular disorders, cardiomyopathies, diabetes, and age-related neurodegenerative diseases. Despite its importance however, we lack a comprehensive understanding of mitochondrial biology. A central challenge arises from the fact that they are semiautonomous organelles with their own genome. Defects in the mitochondrial genome constitute a large fraction of the mitochondrial disorders. In addition, several important biological phenomena ranging from aging to the evolutionary process of speciation are associated with the mitochondrial genome. Given these reasons, the Patel Lab is devoted to studying questions pertaining to the homeostatic regulation of the mitochondrial genome. We employ the tiny but mighty nematode C. elegans for our research. The lab started out using the evolutionary theory of genetic conflict to launch empirical studies into mitochondrial genome. Subsequently, the lab’s work expanded and there are currently four major research efforts underway in the lab:

I. Understand the selection forces that determine the evolution and spread of mutant mitochondrial genomes in populations.

II. Determine the mechanisms that lead to different levels of mutant mitochondrial genomes between cell types.

III. Understand how cells control mitochondrial genome copy number.

IV. Characterize cellular response to defects in mitochondrial RNA processing.

While these four areas of research are connected via a common thread, they span the gamut of scales from evolutionary to mechanistic. In the short-term, we hope that our efforts will provide fundamental insights into mechanisms of mitochondrial genome homeostasis and the consequences of its breakdown. In the long-term, we believe that our broad approach will allow us to gain deep insights into why and under what physiological circumstances the mitochondrial genome homeostasis collapses.