Uncoupling Protein, UCP-4 May Be Involved in Neuronal Defects During Aging and Resistance to Pathogens in Caenorhabditis elegans.

Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins that function to dissipate proton motive force and mitochondrial membrane potential. One UCP has been identified in Caenorhabditis elegans (C. elegans), namely UCP-4. In this study, we examined its expression and localization using a GFP marker in C. elegans. ucp-4 was expressed throughout the body from early embryo to aged adult and UCP-4 was localized in the mitochondria. It is known that increased mitochondrial membrane protential leads to a reactive oxygen species (ROS) increase, which is associated with age-related diseases, including neurodegenerative diseases in humans. A ucp-4 mutant showed increased mitochondrial membrane protential in association with increased neuronal defects during aging, and the neurons of ucp-4 overexpressing animals showed decreased neuronal defects during aging. These results suggest that UCP-4 may be involved in neuroprotection during aging via relieving mitochondrial membrane protential. We also investigated the relationship between UCP-4 and innate immunity because increased ROS can affect innate immunity. ucp-4 mutant displayed increased resistance to the pathogen Staphylococcus aureus compared to wild type. The enhanced immunity in the ucp-4 mutant could be related to increased mitochondrial membrane protential, presumably followed by increased ROS. In summary, UCP-4 might have an important role in neuronal aging and innate immune responses through mediating mitochondrial membrane protential.

pxn-1 and pxn-2 May Interact Negatively during Neuronal Development and Aging in C. elegans.

C. elegans has two functional peroxidasins (PXN), PXN-1 and PXN-2. PXN-2 is essential to consolidate the extracellular matrix during development and is suggested to interact with PXN-1 antagonistically. pxn-1 is involved in neuronal development and possibly maintenance; therefore, we investigated the relationship between pxn-1 and pxn-2 in neuronal development and in aging. During neuronal development, defects caused by pxn-1 overexpression were suppressed by overexpression of both pxn-1 and pxn-2. In neuronal aging process, pxn-1 mutants showed less age-related neuronal defects, such as neuronal outgrowth, neuronal wavy processes, and enhanced short-term memory performance. In addition, pxn-2 overexpressing animals retained an intact neuronal morphology when compared with age-matched controls. Consistent with these results, overexpression of both pxn-1 and pxn-2 restored the severe neuronal defects present with pxn-1 overexpression. These results implied that there is a negative relationship between pxn-1 and pxn-2 via pxn-1 regulating pxn-2. Therefore, pxn-1 may function in neuronal development and age-related neuronal maintenance through pxn-2.