Cytosolic dependent translation supports mitochondrial RNA processing.

Mitochondrial biogenesis relies on both the nuclear and mitochondrial genomes, and imbalance in their expression can lead to inborn errors of metabolism, inflammation, and aging. Here, we investigate N6AMT1, a nucleo-cytosolic methyltransferase that exhibits genetic codependency with mitochondria. We determine transcriptional and translational profiles of and report that it is required for the cytosolic translation of TRMT10C (MRPP1) and PRORP (MRPP3), two subunits of the mitochondrial RNAse P enzyme.

Cytosine methylation flags mitochondrial RNA for degradation.

Mitochondrial double-stranded RNA (dsRNA) can form spontaneously in mitochondria, blocking mitochondrial gene expression and triggering an immune response. A recent study by Kim, Tan, et al. identified a safeguard mechanism in which NOP2/Sun RNA methyltransferase 4 (NSUN4)-mediated RNA methylation (mC) recruits the RNA degradation machinery to prevent dsRNA formation.

ChREBPβ is dispensable for the control of glucose homeostasis and energy balance.

Impaired glucose metabolism is observed in obesity and type 2 diabetes. Glucose controls gene expression through the transcription factor ChREBP in liver and adipose tissues. Mlxipl encodes 2 isoforms: ChREBPα, the full-length form (translocation into the nucleus is under the control of glucose), and ChREBPβ, a constitutively nuclear shorter form.

Hormone-sensitive lipase: sixty years later.

Hormone-sensitive lipase (HSL) was initially characterized as the hormonally regulated neutral lipase activity responsible for the breakdown of triacylglycerols into fatty acids in adipose tissue. This review aims at providing up-to-date information on structural properties, regulation of expression, activity and function as well as therapeutic potential. The lipase is expressed as different isoforms produced from tissue-specific alternative promoters.

Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity.

Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6.

nSMase2 (Type 2-Neutral Sphingomyelinase) Deficiency or Inhibition by GW4869 Reduces Inflammation and Atherosclerosis in Apoe Mice.

Objective: Atherosclerosis is a chronic multifactorial and inflammatory disease of large and medium arteries and the leading cause of cardiovascular diseases worldwide. The aim of this study was to investigate whether and how the nSMase2 (type 2-neutral sphingomyelinase), a key enzyme of sphingolipid metabolism, may contribute to the development of atherosclerotic lesions.

Approach And Results: The role of nSMase2 in atherosclerosis was investigated in mice, mutant for nSMase2, and in mice intraperitoneally injected with GW4869, a pharmacological nSMase2 inhibitor.