Characterizing the interdependencies of mitochondrial fission and fusion machineries and the endoplasmic reticulum

Undergraduate Honors Thesis

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Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/1g05fd10n

Abstract

Mitochondria are one of the most important organelles in the cell. One of their more crucial roles is to produce ATP required for normal cellular function. Interestingly, mitochondria are highly dynamic, undergoing frequent fission or fusion events such that they more closely resemble a network than a group of individual mitochondria. These frequent fission and fusion events allow mitochondria to adapt their morphology to the metabolic demands of the cell. A failure of mitochondria to adjust their lengths appropriately can result in disease. The endoplasmic reticulum helps to orchestrate fission and fusion at ER-mitochondria membrane contact sites, or MCSs. At these ER-mitochondria MCSs, the ER facilitates the recruitment of proteins such as Drp1 and Mfn1 to facilitate mitochondrial fission or fusion, respectively. The presence of ER-mitochondria MCSs at these mitochondrial fission and fusion events suggested that there are specific ER proteins involved in facilitating these processes. By using proximal proteomics, ER proteins potentially involved in mitochondrial dynamics were identified and investigated. It was also discovered that Drp1 and Mfn1 colocalize at these MCSs despite having opposite functions, and data from this study suggests that Drp1, may have a role in Mfn1 recruitment and possibly mitochondrial fusion.

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