E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia

Acute lung injury (ALI) is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it is unknown how these events are linked on the molecular level. Cardiolipin, a mitochondrial-specific lipid, is generated by cardiolipin synthase (CLS1). Here, we show that S.aureus activates a ubiquitin E3 ligase component, Fbxo15, that is sufficient to mediate proteasomal degradation of CLS1 in epithelia, resulting in decreased cardiolipin availability and disrupted mitochondrial function. CLS1 is destabilized by the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), which binds CLS1 to phosphorylate and regulates CLS1 disposal. Like Fbxo15, PINK1 interacts with and regulates levels of CLS1 through a mechanism dependent upon Thr219. S.aureus infection upregulates this Fbxo15-PINK1 pathway to impair mitochondrial integrity, and Pink1 knockout mice are less prone to S.aureus-induced ALI. Thus, ALI-associated disruption of cellular bioenergetics involves bioeffectors that utilize a phosphodegron to elicit ubiquitin-mediated disposal of a key mitochondrial enzyme. © 2014 The Authors

Living with a sibling who suffers from an eating disorder: a pilot interview study

Carina Callio, Sanna Aila Gustafsson Faculty of Medicine and Health, University Health Care Research Center, Region Örebro County, Örebro University, Örebro, Sweden Background and objective: Having a sibling who suffers from an eating disorder (ED) has a profound effect on healthy siblings’ own health, quality of life and family relationships, yet siblings have been an excluded group within health care, and there is a lack of knowledge regarding healthy siblings’ needs and wishes for information and support. Thus, the aim of this study was to examine adolescents’ experiences of living with a sibling who suffers from an ED. Method: In this small-scale pilot study, three boys and two girls aged 15–20 years were interviewed, and the interviews were analyzed by qualitative content analysis. Results: This study confirms prior knowledge of adolescents’ experiences of living with a sibling who is suffering from an ED. The adolescents were concerned about their siblings and lacked information about their siblings’ illness and treatment progress. The girls described that their everyday life had been heavily influenced by their sisters’ illness, while the boys described that their everyday life with friends and activities were not affected to such a great extent. One new result that emerged as something positive was that some informants described that although the ED was a source of conflict in the family, it had led to greater awareness of the importance of gaining sufficient energy and had contributed to better meal situations in the family. Conclusion: Having a sibling with an ED had a profound and negative effect on family relationships, and was often a source of conflict, especially around mealtime. However, it appeared that if parents were able to organize family meals and create an open and supportive climate, the negative effects for the family could be reduced. The health care professionals need to acknowledge the siblings’ need for information and support, and support parents in their important role of caring for well siblings. Keywords: eating disorders, adolescents, siblings, famil