Peroxisomes are ubiquitous organelles that proliferate under different physiological conditions and can form de novo in cells that lack them. The endoplasmic reticulum (ER) has been shown to be the source of peroxisomes in yeast and plant cells. It remains unclear, however, whether the ER has a similar role in mammalian cells and whether peroxisome division or outgrowth from the ER maintains peroxisomes in growing cells. We use a new in cellula pulse-chase imaging protocol with photoactivatable GFP to investigate the mechanism underlying the biogenesis of mammalian peroxisomes. We provide direct evidence that peroxisomes can arise de novo from the ER in both normal and peroxisome-less mutant cells. We further show that PEX16 regulates this process by being cotranslationally inserted into the ER and serving to recruit other peroxisomal membrane proteins to membranes. Finally, we demonstrate that the increase in peroxisome number in growing wild-type cells results primarily from new peroxisomes derived from the ER rather than by division of preexisting peroxisomes.

BackgroundHeart rate recovery (HRR) is a noninvasive assessment of autonomic dysfunction and has been implicated with risk of cardiovascular events and all‐cause mortality. However, evidence has not been systematically assessed. We performed a meta‐analysis of prospective cohort studies to quantify these associations in the general population.Methods and ResultsA literature search using 3 databases up to August 2016 was conducted for studies that reported hazard ratios with 95% CIs for the association between baseline HRR and outcomes of interest. The overall hazard ratios were calculated using a random‐effects model. There were 9 eligible studies in total, with 5 for cardiovascular events enrolling 1061 cases from 34 267 participants, and 9 for all‐cause mortality enrolling 2082 cases from 41 600 participants. The pooled hazard ratios associated with attenuated HRR versus fast HRR that served as the referent were 1.69 (95% CI 1.05–2.71) for cardiovascular events and 1.68 (95% CI 1.51–1.88) for all‐cause mortality. For every 10 beats per minute decrements in HRR, the hazard ratios were 1.13 (95% CI 1.05–1.21) and 1.09 (95% CI 1.01–1.19), respectively. Further analyses suggested that the associations observed between attenuated HRR and risk of fatal cardiovascular events and all‐cause mortality were independent of traditional metabolic factors for cardiovascular disease (all P<0.05).ConclusionsAttenuated HRR is associated with increased risk of cardiovascular events and all‐cause mortality, which supports the recommendation of recording HRR for risk assessment in clinical practice as a routine.

In yeasts and mammals, PEX10 encodes an integral membrane protein with a C3HC4 RING finger motif in its C-terminal domain and is required for peroxisome biogenesis and matrix protein import. In humans, its dysfunction in peroxisome biogenesis leads to severe Zellweger Syndrome and infantile Refsum disease. Here we show that dysfunction of a homologous gene in Arabidopsis leads to lethality at the heart stage of embryogenesis, impairing the biogenesis of peroxisomes, lipid bodies, and protein bodies. In a T-DNA insertion mutant disrupting the fourth exon of the Ath-PEX10 gene, ultrastructural analyses fail to detect peroxisomes characteristic for wild-type embryogenesis. Storage triacyl glycerides are not assembled into lipid bodies (oil bodies; oleosomes) surrounded by the phospholipid-protein monolayer membrane. Instead, the dysfunctional monolayer membranes, which derive from the bilayer membrane of the endoplasmic reticulum, accumulate in the cytosol. Concomitantly the transfer of the storage proteins from their site of synthesis at the endoplasmic reticulum to the vacuoles is disturbed. The mutant can be rescued by transformation with wild-type AthPEX10 cDNA. Transformants of wild-type Hansenula polymorpha cells with the AthPEX10 cDNA did produce the encoded protein without targeting it to peroxisomes. Additionally, the cDNA could not complement a Hansenula pex10 mutant unable to form peroxisomes. The ultrastructural knockout phenotype of AthPEX10p suggests that this protein in Arabidopsis is essential for peroxisome, oleosome, and protein transport vesicle formation.

Background and aimsExercise training is considered a cornerstone in the management of type 2 diabetes, which is associated with impaired endothelial function. However, the association of exercise training with endothelial function in type 2 diabetes patients has not been fully understood. This meta-analysis aimed to investigate their associations with focus on exercise types.MethodsDatabases were searched up to January 2018 for studies evaluating the influences of exercise training with durations ≥ 8 weeks on endothelial function assessed by flow-mediated dilation (FMD) among type 2 diabetes patients or between type 2 diabetics and non-diabetics. Data were pooled using random-effects models to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs).ResultsSixteen databases were included. Exercise training resulted in an overall improvement in FMD by 1.77% (95% CI 0.94–2.59%) in type 2 diabetes patients. Specifically, both aerobic and combined aerobic and resistance exercise increased FMD by 1.21% (95% CI 0.23–2.19%) and 2.49% (95% CI 1.17–3.81%), respectively; but resistance exercise only showed a trend. High-intensity interval aerobic exercise did not significantly improve FMD over moderate-intensity continuous exercise. Notably, the improvement in FMD among type 2 diabetes patients was smaller compared with non-diabetics in response to exercise training (WMD − 0.72%, 95% CI − 1.36 to − 0.08%) or specifically to aerobic exercise (WMD − 0.65%, 95% CI − 1.31 to 0.01%).ConclusionsExercise training, in particular aerobic and combined exercise, improves endothelial function in type 2 diabetes patients, but such an improvement appears to be weakened compared with non-diabetics.Trial registration PROSPERO CRD42018087376Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0711-2) contains supplementary material, which is available to authorized users.