Inhibition of mitochondrial LonP1 protease by allosteric blockade of ATP binding and hydrolysis via CDDO and its derivatives.

The mitochondrial protein LonP1 is an ATP-dependent protease that mitigates cell stress and calibrates mitochondrial metabolism and energetics. Biallelic mutations in the LONP1 gene are known to cause a broad spectrum of diseases, and LonP1 dysregulation is also implicated in cancer and age-related disorders. Despite the importance of LonP1 in health and disease, specific inhibitors of this protease are unknown.

Acetylation and phosphorylation of human TFAM regulate TFAM-DNA interactions via contrasting mechanisms.

Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression and transmission of mitochondrial DNA (mtDNA). However, mechanisms for the post-translational regulation of TFAM are poorly understood. Here, we show that TFAM is lysine acetylated within its high-mobility-group box 1, a domain that can also be serine phosphorylated.

CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+ Lon protease.

CODAS syndrome is a multi-system developmental disorder characterized by cerebral, ocular, dental, auricular, and skeletal anomalies. Using whole-exome and Sanger sequencing, we identified four LONP1 mutations inherited as homozygous or compound-heterozygous combinations among ten individuals with CODAS syndrome. The individuals come from three different ancestral backgrounds (Amish-Swiss from United States, n = 8; Mennonite-German from Canada, n = 1; mixed European from Canada, n = 1).

Segregation of sperm subpopulations in normozoospermic infertile men.

Sperm function is essential for fertilization and embryogenesis yet semen contain a heterogeneous population of sperm. This study was designed to evaluate two different sperm populations separated by the density gradient method. Semen from 25 idiopathic normozoospermic infertile men was processed by double density gradient centrifugation and evaluated for sperm present in the 50% (upper) layer and the 90% (lower) layer for reactive oxygen species (ROS), sperm chromatin integrity, and morphology.

Clinical significance of sperm DNA damage threshold value in the assessment of male infertility.

Sperm DNA integrity is a prerequisite for normal spermatozoal function. The aim of the study was to evaluate the role of sperm chromatin damage, its cut-off level and its effect on sperm parameters in men with idiopathic infertility by analyzing 100 idiopathic infertile men and 50 fertile controls. Semen samples were analyzed as per WHO 1999 guidelines and sperm chromatin structure assay (SCSA) was applied to measure DNA fragmentation index (DFI) in sperm.