Biomedical subjects

Anna Rita Bellu

Publications and source records attributed to Anna Rita Bellu.

4 recordsLinked to original sources

PubMed2004

Cold-inducible selective degradation of peroxisomes in Hansenula polymorpha.

Exposure of Hansenula polymorpha cells, grown in batch cultures on methanol at 37 degrees C, to a cold treatment (18 degrees C) is paralleled by a rapid degradation of peroxisomes present in these cells. Remarkably, the events accompanying organelle degradation at 18 degrees C are similar to those of selective glucose-induced peroxisome degradation in wild-type cells, described before. This observation was strengthened by the finding that cold-induced peroxisome degradation was not observed in mutants impaired in selective peroxisome degradation (Atg(-) mutants). Biochemical data indicated that the onset of peroxisome degradation was not triggered by the inactivation of peroxisome function due to the fall in temperature. We show that our findings have implications in case of fluorescence microscopy studies that are generally not conducted at physiological temperatures and thus may lead to strong morphological alterations unless proper precautions are taken.

Alcohol Dehydrogenase↗

PubMed2003

ALG2, the Hansenula polymorpha isocitrate lyase gene.

To set the basis for molecular and cellular studies of the glyoxylate cycle in methylotrophic yeasts, we isolated and characterized ALG2, the Hansenula polymorpha isocitrate lyase gene. Complementation work and sequence analysis revealed an ORF of 1458 nucleotides, encoding a 486 amino acid protein with a predicted molecular mass of 54.9 kDa. This protein is shorter than the Saccharomyces cerevisiae and Candida tropicalis ICLs, lacks a PST1 signal and possesses a PTS2-like signal. The transcriptional regulation of ALG2 mRNA levels by carbon source is mainly achieved by glucose repression-derepression, whereas ethanol induction plays only a minor role. We present evidence indicating that, in H. polymorpha, neither isocitrate lyase activity nor the ALG2 gene product are necessary for C(1)-peroxisome degradation triggered by ethanol. Therefore, the involvement of glyoxylate in degradation, as described by Kulachkovsky et al. (1997) for Pichia methanolica, does not necessarily apply to all methylotrophic yeasts. The relevant nucleotide sequence has been deposited at GenBank (Accession No. AF373067.1).

Amino Acid Sequence↗

PubMed2003

Selective degradation of peroxisomes in yeasts.

In the last two decades, much progress has been made in understanding the process of induction and biogenesis of peroxisomes, essential organelles in all eukaryotes. Only relatively recently, the first molecular studies on the selective degradation of this important organelle-a process known as pexophagy, which occurs when the organelles have become redundant-have been performed, especially using methylotrophic yeasts. The finding that pexophagy and other transport pathways to the vacuole (vacuolar protein sorting, autophagy, cytoplasm-to-vacuole-targeting and endocytosis) utilize common but also unique genes has placed pexophagy in the heart of the machinery that recycles cellular material. The quest is now on to understand how peroxisome degradation has become such a highly selective process and what the signals are that trigger it. In addition, because the prime determinant of pexophagy is located on the peroxisome itself, it has become essential to study the role of peroxisomal membrane proteins in the degradation process in detail. This review highlights the main achievements of the last years.

Biological Transport↗

PubMed2002

Removal of Pex3p is an important initial stage in selective peroxisome degradation in Hansenula polymorpha.

Selective degradation of peroxisomes (macropexophagy) in Hansenula polymorpha involves the sequestration of individual organelles to be degraded by membranes prior to the fusion of this compartment with the vacuole and subsequent degradation of the whole organelle by vacuolar hydrolases. Here we show that Pex3p, a peroxisomal membrane protein essential for peroxisome biogenesis, escapes this autophagic process. Upon induction of macropexophagy, Pex3p is removed from the organelle tagged for degradation prior to its sequestration. Our data indicate that Pex3p degradation is essential to allow the initiation of the organellar degradation process. Also, in a specific peroxisome degradation-deficient (pdd) mutant in which sequestration still occurs but the vacuolar fusion event is disturbed, the turnover of Pex3p is still observed. Taken together, our data suggest that degradation of Pex3p is part of the initial degradation machinery of individual peroxisomes.

ATP-Binding Cassette Transporters↗