MTFP1 controls mitochondrial fusion to regulate inner membrane quality control and maintain mtDNA levels.

Mitochondrial dynamics play a critical role in cell fate decisions and in controlling mtDNA levels and distribution. However, the molecular mechanisms linking mitochondrial membrane remodeling and quality control to mtDNA copy number (CN) regulation remain elusive. Here, we demonstrate that the inner mitochondrial membrane (IMM) protein mitochondrial fission process 1 (MTFP1) negatively regulates IMM fusion. Moreover, manipulation of mitochondrial fusion through the regulation of MTFP1 levels results in mtDNA CN modulation. Mechanistically, we found that MTFP1 inhibits mitochondrial fusion to isolate and exclude damaged IMM subdomains from the rest of the network. Subsequently, peripheral fission ensures their segregation into small MTFP1-enriched mitochondria (SMEM) that are targeted for degradation in an autophagic-dependent manner. Remarkably, MTFP1-dependent IMM quality control is essential for basal nucleoid recycling and therefore to maintain adequate mtDNA levels within the cell.

Using Cariprazine to Ameliorate Negative Symptoms and Metabolic Side Effects of Clozapine and Paliperidone - Clinical Cases.

Introduction: Cariprazine is a third-generation antipsychotic approved in Europe in 2017 for the treatment of schizophrenia. It presents distinct pharmacodynamic properties, such as D3/D2 partial agonism, preferential binding to D3 receptors, antagonism at the serotonin 5-HT2A and 5-HT2B receptors, partial agonism at 5-HT1A receptors, and low affinity to other receptors (including noradrenergic, histaminergic, and cholinergic). It has demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia with a safe side effect and metabolic profile. Methods: Here, we describe one clinical case of a patient that benefited from an add-on of cariprazine to a regimen of clozapine; and two clinical cases of patients that benefited from the switch from clozapine and paliperidone long-acting injectable to cariprazine. Results and Discussion: Those cases illustrate how cariprazine can be used in patients with schizophrenia in the treatment of both positive and negative symptoms, and when aiming to ameliorate the metabolic burden associated with other treatments. However, further studies are needed to consubstantiate those findings.

Determination of muscle protein synthesis rates in fish using (2)H2O and (2)H NMR analysis of alanine.

Following administration of deuterated water ((2)H2O), the fractional synthetic rate (FSR) of a given endogenous protein can be estimated by (2)H-enrichment quantification of its alanine residues. Currently, this is measured by mass spectrometry following a derivatization procedure. Muscle FSR was measured by (1)H/(2)H NMR analysis of alanine from seabass kept for 6 days in 5% (2)H-enriched saltwater, following acid hydrolysis and amino acid isolation by cation-exchange chromatography of muscle tissue. The analysis is simple and robust, and provides precise measurements of excess alanine (2)H-enrichment in the 0.1-0.4% range from 50 mmol of alanine recovered from muscle protein.