A proteolytic cascade ensures that OMA1 cleaves and inactivates mitochondrial fusion protein OPA1 in times of stress, preventing damaged mitochondria from fusing with healthy organelles. (See also companion paper from Ehses et al. in this issue.)

Mitochondria are widely distributed via regulated transport in neurons, but their sites of biogenesis remain uncertain. Most mitochondrial proteins are encoded in the nuclear genome, and evidence has suggested that mitochondrial DNA (mtDNA) replication occurs mainly or entirely in the cell body. However, it has also become clear that nuclear-encoded mitochondrial proteins can be translated in the axon and that components of the mitochondrial replication machinery reside there as well. We assessed directly whether mtDNA replication can occur in the axons of chick peripheral neurons labeled with 5-bromo-2′-deoxyuridine (BrdU). In axons that were physically separated from the cell body or had disrupted organelle transport between the cell bodies and axons, a significant fraction of mtDNA synthesis continued. We also detected the mitochondrial fission protein Drp1 in neurons by immunofluorescence or expression of GFP-Drp1. Its presence and distribution on the majority of axonal mitochondria indicated that a substantial number had undergone recent division in the axon. Because the morphology of mitochondria is maintained by the balance of fission and fusion events, we either inhibited Drp1 expression by RNAi or overexpressed the fusion protein Mfn1. Both methods resulted in significantly longer mitochondria in axons, including many at a great distance from the cell body. These data indicate that mitochondria can replicate their DNA, divide, and fuse locally within the axon; thus, the biogenesis of mitochondria is not limited to the cell body.

Background This study aimed to compare the effects of sesame (SO), canola (CO), and sesame‐canola (SCO: a blend) oils on glycaemic control markers and liver function enzymes in adults with type 2 diabetes. Methods In this randomized, triple‐blind, three‐way, cross‐over clinical trial, participants replaced their usual oil with the intervention oils for 9 weeks. Serum fasting blood sugar, fasting serum insulin (FSI), insulin resistance (HOMA2‐IR), beta‐cell function (HOMA2‐%B), insulin sensitivity (HOMA2‐%S), quantitative insulin sensitivity check index (QUICKI), as well as serum liver function enzymes were measured at baseline and end of intervention periods. Results Ninety‐two participants completed all treatment periods. After adjusting for confounders, all treatment oils resulted in significant improvements in FSI and HOMA2‐%S (p < 0.05). SO and SCO led to favourable changes in HOMA2‐IR and QUICKI (p < 0.05). Following CO and SCO, there was a significant decrease in HOMA2‐%B (p < 0.05). The sex‐stratified analysis revealed that FSI and HOMA2‐IR were decreased after SO compared to CO in males (p = 0.024). Serum gamma‐glutamyltransferase (GGT) was significantly lower following SO compared to CO in females (p = 0.02), however, the difference in change values was not significant (p = 0.058). Conclusions SO consumption appears to improve glycaemic control markers in males and serum GGT in females compared with CO in patients with type 2 diabetes (registration code: IRCT2016091312571N6).

CM provides either similar or superior results when compared to placebo or other recovery drinks. Overall, the evidence is limited and high-quality clinical trials with more well-controlled methodology and larger sample sizes are warranted.

Ataxia telangiectasia is a devastating neurodegenerative disease caused primarily by loss of function mutations in ATM, a hierarchical DNA repair gene and tumour suppressor. So far, murine models of ataxia telangiectasia have failed to accurately recapitulate many aspects of the disease, most notably, the progressive cerebellar ataxia. Here we present a model of human ataxia telangiectasia using induced pluripotent stem cells, and show that small molecule read-through compounds, designed to induce read-through of mRNA around premature termination codons, restore ATM activity and improve the response to DNA damage. This platform allows for efficient screening of novel compounds, identification of target and off-target effects, and preclinical testing on relevant cell types for the pathogenic dissection and treatment of ataxia telangiectasia.