Knockdown of apoptosis-inducing factor disrupts function of respiratory complex I

Recent findings suggest that apoptotic protein apoptosis-inducing factor (AIF) may also play an important non-apoptotic function inside mitochondria. AIF was proposed to be an important component of respiratory chain complex I that is the major producer of superoxide radical. The possible role of AIF is still controversial. Superoxide production could be used as a valuable measure of complex I function, because the majority of superoxide is produced there. Therefore, we employed superoxide-specific mitochondrial fluorescence dye for detection of superoxide production. We studied an impact of AIF knockdown on function of mitochondrial complex I by analyzing superoxide production in selected cell lines. Our results show that tumoral telomerase-positive (TP) AIF knockdown cell lines display significant increase in superoxide production in comparison to control cells, while a non-tumoral cell line and tumoral telomerase-negative cell lines with alternative lengthening of telomeres (ALT) show a decrease in superoxide production. According to these results, we can conclude that AIF knockdown disrupts function of complex I and therefore increases the superoxide production in mitochondria. The distinct effect of AIF depletion in various cell lines could result from recently discovered activity of telomerase in mitochondria of TP cancer cells, but this hypothesis needs further investigation.

Model of chromosome associations in Mus domesticus spermatocytes

Understanding the spatial organization of the chromosomes in meiotic nuclei is crucial to our knowledge of the genome's functional regulation, stability and evolution. This study examined the nuclear architecture of Mus domesticus 2n=40 pachytene spermatocytes, analyzing the associations among autosomal bivalents via their Centromere Telomere Complexes (CTC). The study developed a nuclear model in which each CTC was represented as a 3D computer object. The probability of a given combination of associations among CTC was estimated by simulating a random distribution of 19 indistinguishable CTC over n indistinguishable "cells" on the nuclear envelope. The estimated association frequencies resulting from this numerical approach were similar to those obtained by quantifying actual associations in pachytene spermatocyte spreads. The nuclear localization and associations of CTC through the meiotic prophase in well-preserved nuclei were also analyzed. We concluded that throughout the meiotic prophase: 1) the CTC of autosomal bivalents are not randomly distributed in the nuclear space; 2) the CTC associate amongst themselves, probably at random, over a small surface of the nuclear envelope, at the beginning of the meiotic prophase; 3) the initial aggregation of centromere regions occurring in lepto-zygotene likely resolves into several smaller aggregates according to patterns of preferential partitioning; 4) these smaller aggregates spread over the inner face of the nuclear envelope, remaining stable until advanced stages of the meiotic prophase or even until the first meiotic division.

Subtelomeric structure of Plasmodium falciparum chromosomes

Previous studies of subtelomeric regions in Plasmodium berghei led to the identification of subtelomeric repeats (2.3kb long) present in a variable number at many chromosomal ends. Both loss and increase in 2.3kb-repeat copy number are involved in chromosome-size polymorphisms. Subtelomeric losses leading to chromosome-size polymorphisms have been described by several authors in P.falciparum where the structure of subtelomeric regions is not known in detail. We therefore undertook their characterisation, by means of chromosome walking and jumping techniques, starting from the telomere-flanking sequence present in pPftel.1, the P.falciparum telomeric clone described by Vernick and McCutchan (1988). The results indicate that at least 20 (out of 28) chromosomal ends in P.falciparum 3D7 chromosomes share a subtelomeric region, about 40kb long, covering (but not limited to) the Rep20 region. Non repetitive, AT-rich portions flanking the Rep20 region on both sides are also conserved at most chromosomal ends.