Sites of close contact between mitochondria and the endoplasmic reticulum (ER) are known as mitochondria-associated membranes (MAM) or mitochondria-ER contacts (MERCs), and play an important role in both cell physiology and pathology. A growing body of evidence indicates that changes observed in the molecular composition of MAM and in the number of MERCs predisposes MAM to be considered a dynamic structure. Its involvement in processes such as lipid biosynthesis and trafficking, calcium homeostasis, reactive oxygen species production, and autophagy has been experimentally confirmed. Recently, MAM have also been studied in the context of different pathologies, including Alzheimer's disease, Parkinson’s disease, amyotrophic lateral sclerosis, type 2 diabetes mellitus and GM1-gangliosidosis. An underappreciated amount of data links MAM with aging or senescence processes. In the present review, we summarize the current knowledge of basic MAM biology, composition and action, and discuss the potential connections supporting the idea that MAM are significant players in longevity.

Studying organelles in isolation has been proven to be indispensable for deciphering the underlying mechanisms of molecular cell biology. However, observing organelles in intact cells with the use of microscopic techniques reveals a new set of different junctions and contact sites between them that contribute to the control and regulation of various cellular processes, such as calcium and lipid exchange or structural reorganization of the mitochondrial network. In recent years, many studies focused their attention on the structure and function of contacts between mitochondria and other organelles. From these studies, findings emerged showing that these contacts are involved in various processes, such as lipid synthesis and trafficking, modulation of mitochondrial morphology, endoplasmic reticulum (ER) stress, apoptosis, autophagy, inflammation and Ca2+ handling. In this review, we focused on the physical interactions of mitochondria with the endoplasmic reticulum and plasma membrane and summarized present knowledge regarding the role of mitochondria-associated membranes in calcium homeostasis and lipid metabolism.

Background: Endocannabinoids can affect pancreatic ␤ cell physiology. Results: Anandamide and 2-arachidonoylglycerol binding to CB 1 receptors induces focal adhesion kinase phosphorylation, which is a prerequisite of insulin release. Conclusion: Focal adhesion kinase activation downstream from CB 1 receptors couples cytoskeletal reorganization to insulin release. Significance: Identifies the molecular blueprint of 2-arachidonoylglycerol signaling in the endocrine pancreas, and outlines a kinase activation cascade linking endocannabinoid signals to insulin release.

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Elevated levels of FFAs, often accompanied by obesity, have been considered as a major risk factor of ␤ -cell failure and insulin resistance, which contributes to the onset and progression of T2D ( 1 ). The FA-induced effect on ␤ -cell integrity and function depends on both the level of FA desaturation and the time of deposition ( 2 ). The prolonged exposure of ␤ -cells to high concentrations of FAs results in an impairment in insulin secretion, a decrease in insulin gene expression, the mitigation of proliferation, and subsequently the induction of lipoapoptosis ( 3 ). The molecular mechanisms that link FAs to ␤ -cell dysfunction still remain to be delineated. Several processes by which FAs mediate lipotoxicity have been suggested, including the generation of reactive oxygen species, de novo ceramide synthesis, endoplasmic reticulum (ER)-associated stress, and alterations in mitochondrial integrity and function ( 4-6 ). Saturated FAs (SFAs) were found to cause more severe effects on the insulin secretory capacity of ␤ -cells and rate of apoptosis compared with MUFAs ( 7,8 ).Stearoyl-CoA desaturase (SCD) is the pivotal lipid metabolism enzyme that catalyzes the biosynthesis of MUFAs by introducing a cis -double bond to a fatty-acyl CoA. The preferred desaturation substrates are palmitic acid (16:0) and stearic acid (18:0), which are converted to palmitoleate (16:1n-7) and oleate (18:1n-9), respectively ( 9 ). The resulting