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1.
Mol Cell ; 84(2): 345-358.e5, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38199007

RESUMO

Cellular proteostasis requires transport of polypeptides across membranes. Although defective transport processes trigger cytosolic rescue and quality control mechanisms that clear translocases and membranes from unproductive cargo, proteins that are synthesized within mitochondria are not accessible to these mechanisms. Mitochondrial-encoded proteins are inserted cotranslationally into the inner membrane by the conserved insertase OXA1L. Here, we identify TMEM126A as a OXA1L-interacting protein. TMEM126A associates with mitochondrial ribosomes and translation products. Loss of TMEM126A leads to the destabilization of mitochondrial translation products, triggering an inner membrane quality control process, in which newly synthesized proteins are degraded by the mitochondrial iAAA protease. Our data reveal that TMEM126A cooperates with OXA1L in protein insertion into the membrane. Upon loss of TMEM126A, the cargo-blocked OXA1L insertase complexes undergo proteolytic clearance by the iAAA protease machinery together with its cargo.


Assuntos
Mitocôndrias , Membranas Mitocondriais , Mitocôndrias/genética , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Biossíntese de Proteínas , Ribossomos/metabolismo , Peptídeo Hidrolases/metabolismo
2.
Methods Mol Biol ; 2643: 13-31, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36952175

RESUMO

Peroxisomes are ubiquitous organelles with essential functions in numerous cellular processes such as lipid metabolism, detoxification of reactive oxygen species, and signaling. Knowledge of the peroxisomal proteome including multi-localized proteins and, most importantly, changes of its composition induced by altering cellular conditions or impaired peroxisome biogenesis and function is of paramount importance for a holistic view on peroxisomes and their diverse functions in a cellular context. In this chapter, we provide a spatial proteomics protocol specifically tailored to the analysis of the peroxisomal proteome of baker's yeast that enables the definition of the peroxisomal proteome under distinct conditions and to monitor dynamic changes of the proteome including the relocation of individual proteins to a different cellular compartment. The protocol comprises subcellular fractionation by differential centrifugation followed by Nycodenz density gradient centrifugation of a crude peroxisomal fraction, quantitative mass spectrometric measurements of subcellular and density gradient fractions, and advanced computational data analysis, resulting in the establishment of organellar maps on a global scale.


Assuntos
Peroxissomos , Saccharomyces cerevisiae , Peroxissomos/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Fracionamento Celular/métodos
3.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 2): 2153-2159, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36452850

RESUMO

Cut neck injury needs prolonged hospitalization, high cost care, reduced quality of life and above all death. Proper exploration is a must in preventing co-morbidities like shock, sepsis, laryngotracheal stenosis or fistula formation. Neck trauma can involve muscles, vessels, nerves, bone and hollow viscera. Though the repair of neck means planning and skill for repair of the structure, the tracheal repair needs special attention to avoid tracheal stenosis. 12 patients were included in the prospective study of 8 months. Management plan was undertaken which were thoroughly studied and discussed with respect to two tracheoplasty cases done in ENT OT, AMCH. Apart from haemodynamic stability all patients were assessed for injury to hollow viscera and planned accordingly as this centre is an important centre for airway reconstruction. Male female ratio was 11:1. Suicidal cut neck injury was the most common cause. Two cases were of tracheal stenosis post tracheostomy. One of the case had associated neurovascular injury but with patent airway. Rest of the cases were repaired under general and/or local anaesthesia. Primary aim should be to maintain airway and to look for the extent of injury to reduce morbidity. Expertise of surgeons' skill is developing every day hence the successfulness of repair will be tested by least of morbidity. From this institute which is skilled in airway reconstruction we could comment that airway reconstruction team should be an integral part of surgeons' team.

4.
Sens Int ; 1: 100052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-34766047

RESUMO

The whole world at present is dealing with the COVID 19 pandemic. As per studies worldwide SARS-CoV-2 by sequencing analysis is 95% homogenous similar to the bat coronavirus and almost 70% similar to the SARS-CoV-1. SARS CoV 2 is a respiratory problem which in its worst form of disease causes ARDS and hampers the patient's ability to breathe on his own and has to be put on Ventilator. As per WHO (World Health Organization) guidelines, sanitization is an effective way of prevention from the infection. The proper sanitization being not feasible and time consuming in certain cases, faster and effective alternatives of sanitization processes are necessary. As per recently published study by researchers in Beijing, China, it was observed that with each degree rise in temperature and percent humidity, the contagiousness of the disease caused by the Coronavirus, named COVID 19 goes down significantly. R-naught or RO can be referred as the average number of people that gets infected from one sick person among a population which is not immune to the virus. The closer to zero an RO value the better the results indicating less spread of the disease. A lower RO means the outbreak is slowing or declining while a higher one means its swelling or growing at faster rate. The RO of the coronavirus hovers between 2 and 2.5 as per World Health Organization or WHO meaning that each new person spreads the disease to about 2.2 people on an average. The chamber being developed is aimed at lowering the Ro value so that the infection rate slows down. RO is not a fixed value, it changes depending on various factors such as proximity among people, the environmental surroundings and climatic conditions. The higher temperatures (38 °C) at 80-90% relative humidity decreases the virus activity within 24 h. Moreover, in a condition where the virus that was dried was stored at higher temperature (>38 °C) and high relative humidity (>95%), there was observed an additional degradation in virus activity at each point in time. Taking into consideration the above research, we developed a COVID De-Incubator chamber to disinfect the clothes and commonly used daily wear items. Our results were exciting as the disinfection proved to be effective at temperatures of 75 °C-80 °C and humidity levels at 80%-90%. Moreover, the chamber was developed at significantly lower costs. In this study, an attempt has been made to fabricate a chamber with temperature and humidity-controlled environment to disinfect daily used material. Using fins and momentum source, a homogenous environment is created inside the chamber for better results, with the help of numerical simulation to decide the optimum angle for the inclination of fins and location of the momentum source.

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