Publication Date

2012-01-13

Availability

Open access

Embargo Period

2012-01-13

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biochemistry and Molecular Biology (Medicine)

Date of Defense

2011-12-16

First Committee Member

Antonio Barrientos

Second Committee Member

Yanbin Zhang

Third Committee Member

Abigail Hackam

Fourth Committee Member

Feng Gong

Fifth Committee Member

Miguel Perez-Pinzon

Sixth Committee Member

Valter Longo

Abstract

Age-related neurodegenerative proteinophaties, including polyglutamine (polyQ) diseases such as Huntington’s disease, are a group of disorders in which a single protein or a set of proteins misfold and aggregate resulting in a progressive and selective loss of anatomically or physiologically related neuronal systems. Despite evidence showing a clear relationship between mitochondrial dysfunction, aging and neurodegenerative proteinophaties, the extent of the mitochondrial respiratory chain deficits, the involvement of mitochondrial dysfunction and the mechanisms responsible for these processes are largely unknown. Using yeast models of cellular aging and polyQ disorders we show that mitochondrial dysfunction is an important contributor to the process of aging and age-related neurodegenerative diseases. Preserving mitochondrial function is essential for standard wild-type aging. Enhancement of mitochondrial biogenesis ameliorates polyQ cytotoxicity and is a required component of interventions that retard the aging process.

Keywords

Mitochondrial Respiration; Yeast Models; Neurodegeneration; Aging

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