Is the maintenance of homeostatic mitochondrial signaling during stress a physiological role for alternative oxidase?
ABSTRACT All plants maintain a non-energy-conserving pathway of mitochondrial electron transport referred to as alternative oxidase (AOX) respiration. Here, we briefly review some of the most prevailing themes for the metabolic and physiological roles of this respiratory pathway. Many of these themes relate to the potential of AOX to provide metabolic homeostasis in response to fluctuating cellular conditions, such as is often seen during stress. We then review reverse genetic experiments that have been used to test these hypotheses. To date, such experiments have been limited to just two dicot species and have only targeted one member (a stress-induced member) of the AOX multigene family. Nonetheless, the experiments to date strongly reinforce the idea that AOX respiration is of particular importance during abiotic and biotic stress. Finally, we propose that another core role of AOX may be to modulate the strength of a stress-signaling pathway from the mitochondrion that controls cellular responses to stress. In this way, AOX could be acting to provide a degree of signaling homeostasis from the mitochondrion. This hypothesis may provide explanation for some of the disparate results seen in reverse genetic experiments regarding the impact of AOX on the reactive oxygen network and oxidative damage.
Article: Comparison of Intact Arabidopsis thaliana Leaf Transcript Profiles during Treatment with Inhibitors of Mitochondrial Electron Transport and TCA Cycle[show abstract] [hide abstract]
ABSTRACT: Plant mitochondria signal to the nucleus leading to altered transcription of nuclear genes by a process called mitochondrial retrograde regulation (MRR). MRR is implicated in metabolic homeostasis and responses to stress conditions. Mitochondrial reactive oxygen species (mtROS) are a MRR signaling component, but whether all MRR requires ROS is not established. Inhibition of the cytochrome respiratory pathway by antimycin A (AA) or the TCA cycle by monofluoroacetate (MFA), each of which initiates MRR, can increase ROS production in some plant cells. We found that for AA and MFA applied to leaves of soil-grown Arabidopsis thaliana plants, ROS production increased with AA, but not with MFA, allowing comparison of transcript profiles under different ROS conditions during MRR. Variation in transcript accumulation over time for eight nuclear encoded mitochondrial protein genes suggested operation of both common and distinct signaling pathways between the two treatments. Consequences of mitochondrial perturbations for the whole transcriptome were examined by microarray analyses. Expression of 1316 and 606 genes was altered by AA and MFA, respectively. A subset of genes was similarly affected by both treatments, including genes encoding photosynthesis-related proteins. MFA treatment resulted in more down-regulation. Functional gene category (MapMan) and cluster analyses showed that genes with expression levels affected by perturbation from AA or MFA inhibition were most similarly affected by biotic stresses such as pathogens. Overall, the data provide further evidence for the presence of mtROS-independent MRR signaling, and support the proposed involvement of MRR and mitochondrial function in plant responses to biotic stress. Copyright: ß 2012 Umbach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by grants from the National Science Foundation (www.nsf.gov; IBN0110768 to J.Y. and L.M. and IOB0344497 and IOS0822521 to D.M.R.) and the United States Department of Energy (www.energy.gov; DEFG0291ER20021 to L.M.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.PLoS ONE 09/2012; 7(9):e44339. · 4.09 Impact Factor
Article: Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.[show abstract] [hide abstract]
ABSTRACT: Paracoccidioides brasiliensis is a human thermal dimorphic pathogenic fungus. Survival of P. brasiliensis inside the host depends on the adaptation of this fungal pathogen to different conditions, namely oxidative stress imposed by immune cells. In this study, we evaluated the role of alternative oxidase (AOX), an enzyme involved in the intracellular redox balancing, during host-P. brasiliensis interaction. We generated a mitotically stable P. brasiliensis AOX (PbAOX) antisense RNA (aRNA) strain with a 70% reduction in gene expression. We evaluated the relevance of PbAOX during interaction of conidia and yeast cells with IFN-γ activated alveolar macrophages and in a mouse model of infection. Additionally, we determined the fungal cell's viability and PbAOX in the presence of H₂O₂. Interaction with IFN-γ activated alveolar macrophages induced higher levels of PbAOX gene expression in PbWt conidia than PbWt yeast cells. PbAOX-aRNA conidia and yeast cells had decreased viability after interaction with macrophages. Moreover, in a mouse model of infection, we showed that absence of wild-type levels of PbAOX in P. brasiliensis results in a reduced fungal burden in lungs at weeks 8 and 24 post-challenge and an increased survival rate. In the presence of H₂O₂, we observed that PbWt yeast cells increased PbAOX expression and presented a higher viability in comparison with PbAOX-aRNA yeast cells. These data further support the hypothesis that PbAOX is important in the fungal defense against oxidative stress imposed by immune cells and is relevant in the virulence of P. brasiliensis.PLoS Neglected Tropical Diseases 10/2011; 5(10):e1353. · 4.69 Impact Factor