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The Role of Mitochondrial Dynamics i...

Machiela, Emily.

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The Role of Mitochondrial Dynamics in Stress Resistance and Neurodegeneration.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Role of Mitochondrial Dynamics in Stress Resistance and Neurodegeneration./
Author:	Machiela, Emily.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	171 p.
Notes:	Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Contained By:	Dissertation Abstracts International79-10B(E).
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10814339
ISBN:	9780355940879

The Role of Mitochondrial Dynamics in Stress Resistance and Neurodegeneration.
Machiela, Emily.

The Role of Mitochondrial Dynamics in Stress Resistance and Neurodegeneration. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 171 p.

Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.

Thesis (Ph.D.)--Van Andel Research Institute, 2018.

This item is not available from ProQuest Dissertations & Theses.

Mitochondria are dynamic, double-membraned organelles responsible for many processes within the cell, including ATP production, calcium buffering, and the stress response. Mitochondria are highly networked throughout the cell and can change shape and size to respond to the energy and stress demands of the cell. These changes are governed by the processes of mitochondrial fission and fusion. Disruptions in mitochondrial dynamics play a role in a variety of diseases, including neurodegenerative diseases such as Parkinson's disease (PD) and Huntington's disease (HD). How these deficits contribute to cellular pathology, however, is still largely unknown. In this work, we investigated the role of mitochondrial morphology and function in stress resistance and neurodegeneration in the nematode C. elegans. We found, using in vivo imaging of the mitochondria, that mitochondrial networks fragment in response to different stresses. Furthermore, mutations in mitochondrial fission and fusion genes alter stress resistance. We also found that in models of PD, dysfunctional mitochondria accumulate with age, and disruption of the mitochondrial unfolded protein response decreases lifespan and worsens phenotypes in these worms. Finally, we also found disrupted mitochondrial networks in worm models of HD and uncover novel mitochondrial targets in HD models that increase lifespan and improve physiologic rates. This work demonstrates the importance of mitochondrial dynamics and function in stress resistance and neurodegenerative disease and identifies novel targets for neurodegenerative disease focusing on mitochondrial dysfunction.

ISBN: 9780355940879Subjects--Topical Terms:

3172791
Cellular biology.

The Role of Mitochondrial Dynamics in Stress Resistance and Neurodegeneration.
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500 $a Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
500 $a Adviser: Jeremy VanRaamsdonk.
502 $a Thesis (Ph.D.)--Van Andel Research Institute, 2018.
506 $a This item is not available from ProQuest Dissertations & Theses.
520 $a Mitochondria are dynamic, double-membraned organelles responsible for many processes within the cell, including ATP production, calcium buffering, and the stress response. Mitochondria are highly networked throughout the cell and can change shape and size to respond to the energy and stress demands of the cell. These changes are governed by the processes of mitochondrial fission and fusion. Disruptions in mitochondrial dynamics play a role in a variety of diseases, including neurodegenerative diseases such as Parkinson's disease (PD) and Huntington's disease (HD). How these deficits contribute to cellular pathology, however, is still largely unknown. In this work, we investigated the role of mitochondrial morphology and function in stress resistance and neurodegeneration in the nematode C. elegans. We found, using in vivo imaging of the mitochondria, that mitochondrial networks fragment in response to different stresses. Furthermore, mutations in mitochondrial fission and fusion genes alter stress resistance. We also found that in models of PD, dysfunctional mitochondria accumulate with age, and disruption of the mitochondrial unfolded protein response decreases lifespan and worsens phenotypes in these worms. Finally, we also found disrupted mitochondrial networks in worm models of HD and uncover novel mitochondrial targets in HD models that increase lifespan and improve physiologic rates. This work demonstrates the importance of mitochondrial dynamics and function in stress resistance and neurodegenerative disease and identifies novel targets for neurodegenerative disease focusing on mitochondrial dysfunction.
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650 4 $a Neurosciences. $3 588700
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