Intraventricular hemorrhage in neonates born from 23 to 26 weeks of gestation: Retrospective analysis of risk factors.

BACKGROUND: The study aim was to determine the incidence and analyze risk factors of IVH stage 3 and 4 in infants born before 26 weeks of gestation. OBJECTIVES: A retrospective analysis of 110 preterm babies (23-26 weeks of gestation) hospitalized from 2009 to 2014 at the Department of Neonatology of Poznan University of Medical Sciences was performed. MATERIAL AND METHODS: In the study group there were 29 (26.4%) children in the 23rd-24th weeks of pregnancy and 81 (73.6%) in the 25th-26th weeks of gestation. RESULTS: Among IVH stage 3 and 4 in neonates without prenatal steroids therapy, OR was 1.616 (1.059- 2.456; p = 0.022) for children born in the 23rd-24th week of gestation and 1.677 (1.001-2.809; p = 0.047) for children born in the 25th-26th week of pregnancy. An analysis of various risk factors revealed the chance of the appearance IVH stage 3 and 4 among neonates born in the 23th-24th and 25th-26th week of gestation rising only among those children who were treated for hypotension with catecholamines (OR 2.031 (0.269-24.21), p = 0.033 and OR 1.989 (0.224-16.55), p = 0.024). CONCLUSIONS: The lower the gestational age, the more frequent the risk of IVH stage 3 and 4. The use of appropriate prophylaxis of perinatal patients (steroids in all pregnant women at risk of preterm birth, limiting the indications for the use of catecholamines for hypotension treatment) reduces the incidence of severe IVH.

Mia40 and MINOS act in parallel with Ccs1 in the biogenesis of mitochondrial Sod1.

Superoxide dismutase 1 (Sod1) is a major superoxide-scavenging enzyme in the eukaryotic cell, and is localized in the cytosol and intermembrane space of mitochondria. Sod1 requires its specific chaperone Ccs1 and disulfide bond formation in order to be retained in the intermembrane space. Our study identified a pool of Sod1 that is present in the reduced state in mitochondria that lack Ccs1. We created yeast mutants with mutations in highly conserved amino acid residues corresponding to human mutations that cause amyotrophic lateral sclerosis, and found that some of the mutant proteins were present in the reduced state. These mutant variants of Sod1 were efficiently localized in mitochondria. Localization of the reduced, Ccs1-independent forms of Sod1 relied on Mia40, an essential component of the mitochondrial intermembrane space import and assembly pathway that is responsible for the biogenesis of intermembrane space proteins. Furthermore, the mitochondrial inner membrane organizing system (MINOS), which is responsible for mitochondrial membrane architecture, differentially modulated the presence of reduced Sod1 in mitochondria. Thus, we identified novel mitochondrial players that are possibly involved in pathological conditions caused by changes in the biogenesis of Sod1.

Dual role of mitofilin in mitochondrial membrane organization and protein biogenesis.

The mitochondrial inner membrane consists of two domains, inner boundary membrane and cristae membrane that are connected by crista junctions. Mitofilin/Fcj1 was reported to be involved in formation of crista junctions, however, different views exist on its function and possible partner proteins. We report that mitofilin plays a dual role. Mitofilin is part of a large inner membrane complex, and we identify five partner proteins as constituents of the mitochondrial inner membrane organizing system (MINOS) that is required for keeping cristae membranes connected to the inner boundary membrane. Additionally, mitofilin is coupled to the outer membrane and promotes protein import via the mitochondrial intermembrane space assembly pathway. Our findings indicate that mitofilin is a central component of MINOS and functions as a multifunctional regulator of mitochondrial architecture and protein biogenesis.