Mitochondrion-processed TERC regulates senescence without affecting telomerase activities

Mitochondrial dysfunctions play major roles in ageing. How mitochondrial stresses invoke downstream responses and how specificity of the signaling is achieved, however, remains unclear. We have previously discovered that the RNA component of Telomerase TERC is imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol. Cytosolic TERC-53 levels respond to mitochondrial functions, but have no direct effect on these functions, suggesting that cytosolic TERC-53 functions downstream of mitochondria as a signal of mitochondrial functions. Here, we show that cytosolic TERC-53 plays a regulatory role on cellular senescence and is involved in cognition decline in 10 months old mice, independent of its telomerase function. Manipulation of cytosolic TERC-53 levels affects cellular senescence and cognition decline in 10 months old mouse hippocampi without affecting telomerase activity, and most importantly, affects cellular senescence in terc cells. These findings uncover a senescence-related regulatory pathway with a non-coding RNA as the signal in mammals.

Mammalian mitochondrial RNAs are degraded in the mitochondrial intermembrane space by RNASET2

Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood. It was long assumed that the degradation happens in the matrix where transcription and translation machineries reside. Here we show that contrary to the assumption, mammalian mitochondrial RNA degradation occurs in the mitochondrial intermembrane space (IMS) and the IMS-localized RNASET2 is the enzyme that degrades the RNAs. This provides a new paradigm for understanding mitochondrial RNA metabolism and transport.

CLINICAL STUDY ON Ca~(2+)-Mg~(2+)-ATP ENZYME ACTIVITY IN RED CELL MEMBRANES OF DIABETIC PATIENTS / 中华内分泌代谢杂志

The basal and calmodulin stimulated Ca2+-Mg2+-ATPase activities in erythrocyte membranes were measured in 40 diabetic patients and 36 normal subjects as control. The results showed that the enzyme activity is significantly decreased in diabetics. The reduction of enzyme activity is inversely related to serum glucose as well as glycosylated hemoglobin. It is suggested that the function of Ca2+-Mg2+-ATPase in red cell membrane of diabetics is decreased. This may be one of the factors causing diabetic microangiopathy. Furthermore, the reduction of enzyme activity might casually be related with hyperglycemia.