Synthesis of New Bodipy Hydrazide Fluorescent Probes for the Detection of Carbonylated Proteins Generated by Oxidative Stress.

Oxidative stress is a cellular disorder implicated in various severe diseases and redox biology and represents an important field of research for the last decades. One of the major consequences of oxidative stress is the carbonylation of proteins, which is also a reliable marker to assess protein oxidative modifications. Accumulation of carbonylated proteins has been associated with aging and age-related diseases and can ultimately causes cell death.

Mitochondrial Lon protease - depleted HeLa cells exhibit proteome modifications related to protein quality control, stress response and energy metabolism.

The ATP-dependent Lon protease is located in the mitochondrial matrix and oxidized proteins are among its primary targets for their degradation. Impairment of mitochondrial morphology and function together with apoptosis were observed in lung fibroblasts depleted for Lon expression while accumulation of carbonylated mitochondrial proteins has been reported for yeast and HeLa Lon deficient cells. In addition, age-related mitochondrial dysfunction has been associated with an impairment of Lon expression.

Proteome Oxidative Modifications and Impairment of Specific Metabolic Pathways During Cellular Senescence and Aging.

Accumulation of oxidatively modified proteins is a hallmark of organismal aging in vivo and of cellular replicative senescence in vitro. Failure of protein maintenance is a major contributor to the age-associated accumulation of damaged proteins that is believed to participate to the age-related decline in cellular function. In this context, quantitative proteomics approaches, including 2-D gel electrophoresis (2-DE)-based methods, represent powerful tools for monitoring the extent of protein oxidative modifications at the proteome level and for identifying the targeted proteins, also referred as to the "oxi-proteome.

Effects of Lon protease down-regulation on the mitochondrial function and proteome.

The Lon protease is an ATP-dependent protease of the mitochondrial matrix that contributes to the degradation of abnormal and oxidized proteins in this compartment. It is also involved in the stability and regulation of the mitochondrial genome. The effects of a depletion of this protease on the mitochondrial function and the identification of oxidized target proteins of Lon have been performed using as cellular model HeLa cells in which Lon level expression can be down-regulated.

Mitochondrial proteases and protein quality control in ageing and longevity.

Mitochondria have been implicated in the ageing process and the lifespan modulation of model organisms. Mitochondria are the main providers of energy in eukaryotic cells but also represent both a major source of reactive oxygen species and targets for protein oxidative damage. Since protein damage can impair mitochondrial function, mitochondrial proteases are critically important for protein maintenance and elimination of oxidized protein.