University of Milano-Bicocca

About: University of Milano-Bicocca is a education organization based out in Milan, Italy. It is known for research contribution in the topics: Population & Blood pressure. The organization has 8972 authors who have published 22322 publications receiving 620484 citations. The organization is also known as: Università degli Studi di Milano-Bicocca & Universita degli Studi di Milano-Bicocca.

OPA1 Processing Reconstituted in Yeast Depends on the Subunit Composition of the m-AAA Protease in Mitochondria

Abstract: The morphology of mitochondria in mammalian cells is regulated by proteolytic cleavage of OPA1, a dynamin-like GTPase of the mitochondrial inner membrane. The mitochondrial rhomboid protease PARL, and paraplegin, a subunit of the ATP-dependent m-AAA protease, were proposed to be involved in this process. Here, we characterized individual OPA1 isoforms by mass spectrometry, and we reconstituted their processing in yeast to identify proteases involved in OPA1 cleavage. The yeast homologue of OPA1, Mgm1, was processed both by PARL and its yeast homologue Pcp1. Neither of these rhomboid proteases cleaved OPA1. The formation of small OPA1 isoforms was impaired in yeast cells lacking the m-AAA protease subunits Yta10 and Yta12 and was restored upon expression of murine or human m-AAA proteases. OPA1 processing depended on the subunit composition of mammalian m-AAA proteases. Homo-oligomeric m-AAA protease complexes composed of murine Afg3l1, Afg3l2, or human AFG3L2 subunits cleaved OPA1 with higher efficiency than paraplegin-containing m-AAA proteases. OPA1 processing proceeded normally in murine cell lines lacking paraplegin or PARL. Our results provide evidence for different substrate specificities of m-AAA proteases composed of different subunits and reveal a striking evolutionary switch of proteases involved in the proteolytic processing of dynamin-like GTPases in mitochondria.

ECMO criteria for influenza A (H1N1)-associated ARDS: role of transpulmonary pressure

Abstract: To assess whether partitioning the elastance of the respiratory system (E RS) between lung (E L) and chest wall (E CW) elastance in order to target values of end-inspiratory transpulmonary pressure (PPLATL) close to its upper physiological limit (25 cmH2O) may optimize oxygenation allowing conventional treatment in patients with influenza A (H1N1)-associated ARDS referred for extracorporeal membrane oxygenation (ECMO). Prospective data collection of patients with influenza A (H1N1)-associated ARDS referred for ECMO (October 2009–January 2010). Esophageal pressure was used to (a) partition respiratory mechanics between lung and chest wall, (b) titrate positive end-expiratory pressure (PEEP) to target the upper physiological limit of PPLATL (25 cmH2O). Fourteen patients were referred for ECMO. In seven patients PPLATL was 27.2 ± 1.2 cmH2O; all these patients underwent ECMO. In the other seven patients, PPLATL was 16.6 ± 2.9 cmH2O. Raising PEEP (from 17.9 ± 1.2 to 22.3 ± 1.4 cmH2O, P = 0.0001) to approach the upper physiological limit of transpulmonary pressure (PPLATL = 25.3 ± 1.7 cm H2O) improved oxygenation index (from 37.4 ± 3.7 to 16.5 ± 1.4, P = 0.0001) allowing patients to be treated with conventional ventilation. Abnormalities of chest wall mechanics may be present in some patients with influenza A (H1N1)-associated ARDS. These abnormalities may not be inferred from measurements of end-inspiratory plateau pressure of the respiratory system (PPLATRS). In these patients, titrating PEEP to PPLATRS may overestimate the incidence of hypoxemia refractory to conventional ventilation leading to inappropriate use of ECMO.