No abstract

Mitochondria-derived vesicles (MDVs) have been shown to transport cargo from the mitochondria to the peroxisomes. Mitochondria and peroxisomes share common functions in the oxidation of fatty acids and the reduction of damaging peroxides. Their biogenesis is also linked through both the activation of master transcription factors such as PGC-1alpha and the common use of fission machinery, including DRP1, Mff, and hFis1. We have previously shown that MDVs are formed independently of the known mitochondrial fission GTPase Drp1 and are enriched for a mitochondrial small ubiquitin-like modifier (SUMO) E3 ligase called MAPL (mitochondrial-anchored protein ligase). Here, we demonstrate that the retromer complex, a known component of vesicle transport from the endosome to the Golgi apparatus, regulates the transport of MAPL from mitochondria to peroxisomes. An unbiased screen shows that Vps35 and Vps26 are found in complex with MAPL, and confocal imaging reveals Vps35 recruitment to mitochondrial vesicles. Silencing of Vps35 or Vps26A leads to a significant reduction in the delivery of MAPL to peroxisomes, placing the retromer within a novel intracellular trafficking route and providing insight into the formation of MAPL-positive MDVs.

Background In rural areas in China and India, cardiovascular disease burden is high but economic and healthcare resources are limited. This study aims to develop and evaluate a simplified cardiovascular management program (SimCard) delivered by community health workers (CHWs) with the aid of a smartphone-based electronic decision support system. Methods and Results The SimCard study was a yearlong cluster-randomized controlled trial conducted in 47 villages (27 in China and 20 in India). 2,086 ‘high cardiovascular risk’ individuals (aged 40 years or older with self-reported history of coronary heart disease, stroke, diabetes, and/or measured systolic blood pressure ≥160 mmHg) were recruited. Participants in the intervention villages were managed by CHWs through an Android-powered “app” on a monthly basis focusing on two medication use and two lifestyle modifications. Compared with the control group, the intervention group had a 25.5% (P<0.001) higher net increase in the primary outcome of the proportion of patient-reported anti-hypertensive medication use pre-and-post intervention. There were also significant differences in certain secondary outcomes: aspirin use (net difference 17.1%, P<0.001) and systolic blood pressure (−2.7 mmHg, P=0.04). However, no significant changes were observed in the lifestyle factors. The intervention was culturally tailored and country-specific results revealed important differences between the regions. Conclusions The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in resource-poor settings in China and India. Larger trials in more places are needed to ascertain potential impacts on mortality and morbidity outcomes. Clinical Trial Registration Information clinicaltrials.gov. Identifier: NCT01503814.