Proteorhodopsin (PR) is present in half of surface ocean bacterioplankton, where its light-driven proton pumping provides energy to cells. Indeed, PR promotes growth or survival in different bacteria. However, the metabolic pathways mediating the light responses remain unknown. We analyzed growth of the PR-containing Dokdonia sp. MED134 (where light-stimulated growth had been found) in seawater with low concentrations of mixed [yeast extract and peptone (YEP)] or single (alanine, Ala) carbon compounds as models for rich and poor environments. We discovered changes in gene expression revealing a tightly regulated shift in central metabolic pathways between light and dark conditions. Bacteria showed relatively stronger light responses in Ala compared with YEP. Notably, carbon acquisition pathways shifted toward anaplerotic CO 2 fixation in the light, contributing 31 ± 8% and 24 ± 6% of the carbon incorporated into biomass in Ala and YEP, respectively. Thus, MED134 was a facultative double mixotroph, i.e., photo-and chemotrophic for its energy source and using both bicarbonate and organic matter as carbon sources. Unexpectedly, relative expression of the glyoxylate shunt genes (isocitrate lyase and malate synthase) was >300-fold higher in the light-but only in Ala-contributing a more efficient use of carbon from organic compounds. We explored these findings in metagenomes and metatranscriptomes and observed similar prevalence of the glyoxylate shunt compared with PR genes and highest expression of the isocitrate lyase gene coinciding with highest solar irradiance. Thus, regulatory interactions between dissolved organic carbon quality and central metabolic pathways critically determine the fitness of surface ocean bacteria engaging in PR phototrophy. microbial ecology | gene expression regulation | quantitative PCR

Proteorhodopsin (PR), a ubiquitous membrane photoprotein in marine environments, acts as a light-driven proton pump and can provide energy for bacterial cellular metabolism. However, knowledge of factors that regulate PR gene expression in different bacteria remains strongly limited. Here, experiments with Vibrio sp. AND4 showed that PR phototrophy promoted survival only in cells from stationary phase and not in actively growing cells. PR gene expression was tightly regulated, with very low values in exponential phase, a pronounced peak at the exponential/stationary phase intersection, and a marked decline in stationary phase. Thus, PR gene expression at the entry into stationary phase preceded, and could therefore largely explain, the stationary phase light-induced survival response in AND4. Further experiments revealed nutrient limitation, not light exposure, regulated this differential PR expression. Screening of available marine vibrios showed that the PR gene, and thus the potential for PR phototrophy, is found in at least three different clusters in the genus Vibrio. In an ecological context, our findings suggest that some PR-containing bacteria adapted to the exploitation of nutrient-rich micro-environments rely on a phase of relatively slowly declining resources to mount a cellular response preparing them for adverse conditions dispersed in the water column.

On the basis of evidences that caspase-2 gene targeting in several generated mouse models accelerates tumor formation, this enzyme was recently implicated in tumor suppression. The observed function, however, compels other molecular perturbations harboring tumorigenic properties. Therefore, the question remains as to whether or not caspase-2 can be considered a true tumor suppressor? The traditional view of caspase-2 being vital for the apoptotic response to induced cell stress in some systems is in line with these findings. Yet, caspase-2 has also been associated with other processes which equally might interfere with tumorigenic potential, including the oxidative stress response, aging and genome surveillance. By different mechanisms, this enzyme has been proposed to function as a checkpoint regulator in the cell cycle. Together, these data indicate that caspase-2 is a highly versatile factor, a view that is contrasted by the alternative explanation where the enzyme harbors a mechanism affecting a discrete process, which in turn is functionally connected to other cell systems. In any case, it is clear that the general view of caspase-2 as a protein mainly involved in apoptotic cell death is shattered. Hence, we wish to discuss the perspectives of recent achievements in caspase-2-related research.

Caspase-2 has been embodied as an initiator or executioner protease in diverse apoptotic scenarios. However, accumulating evidence is challenging this view, pertaining to its true role. The enzyme's catalytic activity is currently implicated in various functions required for correct cell proliferation, such as counteracting genomic instability, as well as suppressing tumorigenesis. Here, apart from summarizing the latest observations in caspase-2-related research, we make an attempt to reconcile these findings and discuss their implications for future directions.

Caspase-2 has been implicated in diverse cellular processes, and the identification of factors with which it interacts has steadily increased. In the present study, we report a direct interaction between caspase-2 and factor associated with neutral sphingomyelinase activation (FAN) using yeast two-hybrid screening and co-immunoprecipitation. Further, stable suppression of caspase-2 expression in HEK293T and HeLa cells enabled a systematic investigation of putative novel enzyme functionalities, especially with respect to ceramide production, cell migration, IL-6 production and vesicular homeostasis, all of which have been previously reported to be associated with FAN. Lipidomics excluded the involvement of caspase-2 in the generation of ceramide species, but caspase-2-dependent deregulation of IL-6 release, vesicular size and delayed cell relocation supported an association between caspase-2 and FAN. Collectively, these data identify a novel caspase-2-interacting factor, FAN, and expand the role for the enzyme in seemingly non-apoptotic cellular mechanisms.