File(s) under permanent embargo

Reason: Restricted by author. A copy can be supplied under Section 51(2) of the Australian Copyright Act 1968 by submitting a document delivery request through your library or by emailing document.delivery@monash.edu

An evolutionary perspective of the trafficking of pathogenic proteins to mitochondria

thesis
posted on 28.02.2017, 00:21 by Tong, Janette Ho Shuen
Mitochondria evolved from the ancestral bacterial endosymbiont whose genes were either integrated into the host nucleus or lost, this gave rise to a novel protein import system in mitochondria. Reclinomonas americana is a unicellular eukaryote and has the most gene-rich mitochondrial genome known. The mitochondrial genome of R. americana encodes a bacterial-like protein transport subunit, SecY, and many mitochondrial-encoded gene products have predicted topologies or signal sequences that would be compatible for SecY-mediated protein export. One such mitochondrial-encoded gene of R. americana, RaCox11, was utilized to examine whether it could be transferred into the nucleus. Biochemical analyses of RaCox11 showed that it could functionally complement a Δcox11 yeast mutant when expressed in the cytosol. This predisposed mitochondrial targeting ability of proteins is one of the underlying possibilities of why many proteins secreted from pathogenic bacteria are also frequently targeted to mitochondria during infection. Many bacterial effector proteins are found frequently targeted to mitochondria during infection, but the import routes into mitochondria are mostly unknown. In this study, the mitochondrial targeting pathways of two pathogenic bacterial proteins, LncP and PVL, have been characterized to be transported by the Tim9:10 chaperone complex at the intermembrane space of mitochondria. From the intermembrane space, they are guided to and assembled into the inner membrane of mitochondria. With the precise localization and targeting pathways of these pathogenic proteins now known, it opens up the possibility to investigate their roles in the modulation of mitochondrial function during bacterial infections.

History

Principal supervisor

Kip Gabriel

Year of Award

2013

Department, School or Centre

Biochemistry and Molecular Biology

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Medicine Nursing and Health Sciences