Braeckman BP et al. (2002) Aging Cell "Rebuttal to Van Voorhies: 'the influence of metabolic rate on longevity in the nematode Caenorhabditis elegans'."

Braeckman BP, Houthoofd K, Vanfleteren JR

[Aging Cell, 2002]

The papers by Van Voorhies in Free Radical Biology & Medicine (33, 587-596, 2002) and in this journal claim that the major longevity-extending mutations in C. elegans essentially act by reducing metabolic rate as predicted by the rate-of-living theory, and do not alter any metabolically independent mechanism specific to aging. In contrast, we found no evidence of a reduction in metabolic rate in these mutants using different experimental approaches. Now, Van Voorhies challenges the accuracy of our experimental results.

Morton DB et al. (1999) Curr Biol "Soluble guanylyl cyclases in Caenorhabditis elegans: NO is not the answer."

Hudson ML, O'Shea M, Waters E, Morton DB

[Curr Biol, 1999]

Guanylyl cyclases (GCs), the enzymes that synthesize cyclic GMP (cGMP), have classically been divided into two groups: receptor GCs and soluble GCs. Receptor GCs are integral membrane proteins such as the retinal guanylyl cyclases and the atrial natriuretic peptide receptors. Soluble GCs are heterodimeric proteins consisting of an alpha and a beta subunit that bind a heme group and are activated by nitric oxide (NO). The recent publication of the Caenorhabditis elegans genomic sequence has revealed an unexpected abundance of GCs.

Lee Y et al. (2008) FEMS Microbiol Lett "The role of disulfide bond isomerase A (DsbA) of Escherichia coli O157:H7 in biofilm formation and virulence."

Yeom S, Kim S, Lee Y, Kim Y, Park W, Park S, Jeon CO

[FEMS Microbiol Lett, 2008]

The role of periplasmic disulfide oxidoreductase DsbA in Shiga toxin-producing Escherichia coli O157:H7 (STEC) was investigated. Deletion of dsbA (DeltadsbA) significantly decreased cell motility and alkaline phosphatase activity in STEC. STEC DeltadsbA also showed greater sensitivity to menadione and under low pH conditions. Significant reductions in surface attachment to both biotic (HT-29 epithelial cells) and abiotic (polystyrene and polyvinyl chloride) surfaces were observed in STEC DeltadsbA. In addition, no biofilm formation was detected in STEC DeltadsbA compared to wild-type cells in glass capillary tubes under continuous flow-culture system conditions. In the nematode model Caenorhabditis elegans-killing assay, the deletion of dsbA in STEC resulted in attenuated virulence compared to wild-type cells. STEC DeltadsbA was also found to have a reduced ability to colonize the nematode gut. These results suggest that DsbA plays important roles in biofilm formation and virulence in STEC cells.

Clark IE et al. (2006) Nature "Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin."

Clark IE, Huh JR, Cao JH, Guo M, Jiang C, Yoo SJ, Dodson MW, Seol JH, Hay BA

[Nature, 2006]

Parkinson''s disease is the second most common neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction has been implicated as an important trigger for Parkinson''s disease-like pathogenesis because exposure to environmental mitochondrial toxins leads to Parkinson''s disease-like pathology. Recently, multiple genes mediating familial forms of Parkinson''s disease have been identified, including PTEN-induced kinase 1 (PINK1; PARK6) and parkin (PARK2), which are also associated with sporadic forms of Parkinson''s disease. PINK1 encodes a putative serine/threonine kinase with a mitochondrial targeting sequence. So far, no in vivo studies have been reported for pink1 in any model system. Here we show that removal of Drosophila PINK1 homologue (CG4523; hereafter called pink1) function results in male sterility, apoptotic muscle degeneration, defects in mitochondrial morphology and increased sensitivity to multiple stresses including oxidative stress. Pink1 localizes to mitochondria, and mitochondrial cristae are fragmented in pink1 mutants. Expression of human PINK1 in the Drosophila testes restores male fertility and normal mitochondrial morphology in a portion of pink1 mutants, demonstrating functional conservation between human and Drosophila Pink1. Loss of Drosophila parkin shows phenotypes similar to loss of pink1 function. Notably, overexpression of parkin rescues the male sterility and mitochondrial morphology defects of pink1 mutants, whereas double mutants removing both pink1 and parkin function show muscle phenotypes identical to those observed in either mutant alone. These observations suggest that pink1 and parkin function, at least in part, in the same pathway, with pink1 functioning upstream of parkin. The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson''s disease pathogenesis.