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Researchers at the University of
California, San Francisco (UCSF) are investigating the function of a protein
called Parkin in TB. Kevan Shokat, PhD, of UCSF and colleagues already were
investigating Parkin’s role in Parkinson’s disease and found that its malfunction
was associated with the loss of nerve cells in Parkinson’s. Jeffery Cox, PhD,
UCSF microbiologist and TB expert, focused on the enzyme Parkin as a common
element in Parkinson’s and TB while investigating how macrophages (immune
cells) surround and destroy bacteria. Cox found that mitophagy, the process of
disposing of worn-out cell mitochondria, depended on Parkin. He then speculated
that Parkin might be useful with TB and the process of xenophagy (the process
by which the macrophage destroys foreign bacteria). Also, he learned that
specific naturally occurring variations (polymorphisms) in the Parkin gene were
associated with increased susceptibility to TB infection.
Cox and colleagues reported that
Parkin triggered destruction of TB bacteria by macrophages. In both mouse and
human macrophages infected with TB in the lab, Parkin had an important role in
fighting the bacteria. The researchers noticed that genetically engineered mice
that lacked Parkin died when infected with TB while those with normal Parkin
levels survived. Cox is studying ways to increase Parkin activity in
TB-infected mice using a method similar to that being used by Shokat to prevent
neurodegeneration in Parkinson’s. Cox is working with Shokat to improve Parkin
activity against cell-invading bacteria.
The full report, “The Ubiquitin
Ligase Parkin Mediates Resistance to Intracellular Pathogens,” was published
online in the journal Nature (2013; doi:10.1038/nature12566).
