Mouse anti-Human SNX4 monoclonal antibody, clone 5I9

The tin(IV) complexes [SnX4L] [L = 2-(2-pyridyl)benzimidazole; X = Cl, Br or I] and [SnMe2Cl2L] were prepared by a dehydration reaction of N-(2-aminophenyl)pyridine-2-carboxamide L' with either SnX4 (X = Cl, Br or I) or SnMe2Cl2 in chloroform solution. The X-ray crystal structures of [SnMe2Cl2L] and [SnBr4L].0.5MeNO2 show a distorted octahedral geometry around the tin(IV) atom in both molecules. The ligand L acts as a bidentate chelate with ligated atoms being the pyridine-type nitrogens of the heterocyclic rings. The chlorine atoms in [SnMe2Cl2L] are cis while the methyl groups are trans to each other. Infrared and Mossbauer spectra and a correlation of X-ray structural and anti-tumour (P388 lymphocytic leukaemia) data for the octahedral tin(IV) complexes are also reported. The X-ray structures are the first such reported for metal complexes containing 2-(2-pyridyl)benzimidazole.

Sorting nexins are a conserved protein family involved in vesicle transport, membrane trafficking and protein sorting. The sorting nexin ATG24/SNX4 has been demonstrated to be involved in different autophagy pathways and in endosomal trafficking. However, its impact on cellular quality control and on aging and development is still elusive. Here we report studies analyzing the function of PaATG24 in the aging model Podospora anserina. Ablation of PaATG24 leads to a reduced growth rate, infertility, and to a pronounced lifespan reduction. These characteristics are accompanied by alterations of the morphology and size distribution of vacuoles and severe impairments in non-selective and selective autophagy of peroxisomes (pexophagy) and mitochondria (mitophagy). While general autophagy and pexophagy are almost completely blocked, a PaATG24-independent form of mitophagy is induced during aging. In the elPaAtg24 mutant a strong accumulation of peroxisomes occurs while mitochondrial abundance is only slightly increased. These mitochondria are partially affected in function. Most strikingly, although some PaATG24-independent mitophagy exists, it appears that this is not sufficient to remove dysfunctional mitochondria efficiently enough to prevent premature aging. Overall our data emphasize the key role of mitochondria in aging and of mitophagy in quality control to keep a population of "healthy" mitochondria during aging.