Effects of Mitochondrial protein degradation on organismal health
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We are interested in understanding the molecular and cell biology that underlies aging. To do this, we use fruit flies as a model organism. Flies are particularly great model organisms for this type of study which combines genetics with physiology phenotypes. Moreover recent estimates suggest that homologs of 75% of disease causing genes in humans are also present in flies.
A current idea for what drives aging is that organisms progressively lose function over their lifetime due to a buildup of damaged biomolecules (like proteins). Mitochondria are particularly important organelles for aging--we think mitochondria are the source of free radicals that cause the damage that results in aging. As a result, we also expect that mitochondria are the organelles that suffer the most from aging-related free radical damage since the free radicals they generate will damage them first.
Our lab is interested in investigating the role that mitochondrial protein damage plays in aging. Recently, we found that increasing the amount of an enzyme involved in protein degradation inside mitochondria can result in healthier, longer lived flies. Our goal is to expand upon these results to gain a better understanding of the relationship that exists between enzymes that help degrade proteins inside mitochondria and organismal health. Specifically, during the summer, we are interested in overexpressing genes that are suspected to be involved in protein degradation in mitochondria. Once we can ascertain whether the overexpression results in (1) increased transcription of the candidate mitochondrial protease, and (2) a measurable increase in mitochondrial protein degradation, we will examine multiple markers of mitochondrial function and fly health. Assessing their effects on mitochondrial functions involves biochemical reactions to measure mitochondrial protein degradation, Krebs cycle activity, electron transport through the electron transport chain, and mitochondrial genome copy number (an indicator of mitochondrial volume). Fly health effects can be assessed by assaying resistance to various stresses (heat, oxidation, diet), mobility (ability to climb, overall activity), and longevity. These results will help us understand whether and how mitochondrial function is a limiting factor for aging and longevity.