Metalloprotease OMA1 Fine-tunes Mitochondrial Bioenergetic Function and Respiratory Supercomplex Stability

Mitochondria are involved in key cellular functions including energy production, metabolic homeostasis, and apoptosis. Normal mitochondrial function is preserved by several interrelated mechanisms. One mechanism – intramitochondrial quality control (IMQC) – is represented by conserved proteases distributed across mitochondrial compartments. Many aspects and physiological roles of IMQC components remain unclear. Here, we show that the IMQC protease Oma1 is required for the stability of the respiratory supercomplexes and thus balanced and tunable bioenergetic function. Loss of Oma1 activity leads to a specific destabilization of respiratory supercomplexes and consequently to unbalanced respiration and progressive respiratory decline in yeast. Similarly, experiments in cultured Oma1-deficient mouse embryonic fibroblasts link together impeded supercomplex stability and inability to maintain proper respiration under conditions that require maximal bioenergetic output. Finally, transient knockdown of OMA1 in zebrafish leads to impeded bioenergetics and morphological defects of the heart and eyes. Together, our biochemical and genetic studies in yeast, zebrafish and mammalian cells identify a novel and conserved physiological role for Oma1 protease in fine-tuning of respiratory function. We suggest that this unexpected physiological role is important for cellular bioenergetic plasticity and may contribute to Oma1- associated disease phenotypes in humans

The relationship between dendritic branch dynamics and CPEB-labeled RNP granules captured <i>in vivo</i>

Cytoplasmic Polyadenylation Element Binding protein (CPEB) is an RNA binding protein involved in dendritic delivery of mRNA and activity-dependent, polyadenylation-induced translation of mRNAs in the dendritic arbor. CPEB affects learning and memory and impacts neuronal morphological and synaptic plasticity. In neurons, CPEB is concentrated in ribonucleoprotein (RNP) granules that distribute throughout the dendritic arbor and localize near synapses. We tagged full-length CPEB and an inactive mutant CPEB, that is incapable of triggering activity-induced mRNA translation, with fluorescent protein, then imaged rapid dendritic branch dynamics and RNP distribution using 2-photon time-lapse microscopy of neurons in the optic tectum of living Xenopus laevis tadpoles. The density of CPEB-containing RNP granules in dendrites is high and the distribution of granules does not correlate with sites of rapid dendritic branch dynamics. Nevertheless, inactive CPEB accumulates in granules in terminal dendritic branches, supporting the hypothesis that upon activation CPEB and its mRNA cargo are released from granules and are then available for dendritic translation

Metalloprotease OMA1 Fine-tunes Mitochondrial Bioenergetic Function and Respiratory Supercomplex Stability

Mitochondria are involved in key cellular functions including energy production, metabolic homeostasis, and apoptosis. Normal mitochondrial function is preserved by several interrelated mechanisms. One mechanism – intramitochondrial quality control (IMQC) – is represented by conserved proteases distributed across mitochondrial compartments. Many aspects and physiological roles of IMQC components remain unclear. Here, we show that the IMQC protease Oma1 is required for the stability of the respiratory supercomplexes and thus balanced and tunable bioenergetic function. Loss of Oma1 activity leads to a specific destabilization of respiratory supercomplexes and consequently to unbalanced respiration and progressive respiratory decline in yeast. Similarly, experiments in cultured Oma1-deficient mouse embryonic fibroblasts link together impeded supercomplex stability and inability to maintain proper respiration under conditions that require maximal bioenergetic output. Finally, transient knockdown of OMA1 in zebrafish leads to impeded bioenergetics and morphological defects of the heart and eyes. Together, our biochemical and genetic studies in yeast, zebrafish and mammalian cells identify a novel and conserved physiological role for Oma1 protease in fine-tuning of respiratory function. We suggest that this unexpected physiological role is important for cellular bioenergetic plasticity and may contribute to Oma1- associated disease phenotypes in humans

A comparative content analysis of media reporting of sports betting in Australia: Lessons for public health media advocacy approaches

© 2017 The Author(s). Background: Harmful gambling is a significant public health issue. There has been widespread discussion in the Australian media about the extent and impact of sports betting on the Australian community, particularly relating to young men and children. Given the role th at the media plays in influencing policy change and political agendas, and the acknowledgement that media based advocacy is a fundamental component of successful advocacy campaigns, this research aimed to investigate how different stakeholder groups discuss sports betting within the Australian print media. The study uses this information to provide recommendations to guide public health media advocacy approaches. Methods: A quantitative content analysis of print media articles was conducted during two significant Parliamentary Inquiries about sports betting - (1) The Joint Select Committee Inquiry into the Advertising and Promotion of Gambling Services in Sport (2012/2013), and (2) 'The Review of Illegal Offshore Wagering (2015/2016). A total of 241 articles from 12 daily Australian newspapers were analysed. Statistical analysis was used to compare frequency of, and changes in, themes, voices and perspectives over time. Results: Discussions about the marketing and communication of sports betting was a main theme in media reporting (n = 165, 68.5%), while discussions about gambling reform decreased significantly across the two time periods (p &lt; 0.0001). The presence of sports betting industry (p &lt; 0.0001), sporting code (p &lt; 0.0001) and public health expert (p = 0.001) voices all increased significantly across the two time periods. There were very few (n = 11, 4.6%) voices from those who had experienced gambling harm. Finally, while there were significantly fewer articles taking the perspective that regulation changes were needed to protect vulnerable sub-populations (p &lt; 0.0001), articles that had a neutral perspective about the need for regulation change increased significantly across the two time periods (p &lt; 0.0001). Discussion and conclusions: Mapping the media reporting of sports betting is important in developing effective public health advocacy approaches. This study indicates that discussions about the marketing strategies utilised by the sports betting industry was still a main theme in media articles. However, discussions relating to sports betting reforms, in particular to protect individuals who may be vulnerable to the harm associated with these products and their promotional strategies (for example children and young men) decreased during the time periods. Public health advocates may seek to address the decrease in media reports about reform by developing clear evidence-based messages about why regulatory reform is needed, as well as the potential consequences of not implementing reforms. Working with organisations to build capacity for people who have experienced gambling harm may help ensure that individuals with a lived experience of harm have an increased voice in the media