Impact of protein degradation on mitochondrial protein import

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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 expression of enzymes 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. If the buildup of damaged proteins in mitochondria are detrimental to health, we expect that decreasing the halflife of mitochondrial proteins by boosting the activity of enzymes involved in mitochondrial protein degradation would improve mitochondrial function and organismal health. This may be limiting, however, if the import of new proteins into the mitochondria to replace the degraded proteins is unable to keep up with the increased demand, and this is an aspect of mitochondrial protein homeostasis that is understudied. For this reason, a primary goal during the summer is to overexpress genes that are suspected to be involved in protein degradation in mitochondria and assessing their effects on mitochondrial protein import. Mitochondrial protein import pathways have not been previously studied in the lab before, and significant effort will be necessary to test, optimize, and apply different ways of measuring mitochondrial protein import. Once established, these results will help us understand how the balance between mitochondrial protein degradation and mitochondrial protein import affect mitochondrial function, and whether and how mitochondrial function impacts organismal health and aging.