11 research outputs found
Identification of intragenic mutations in the Hansenula polymorpha PEX6 gene that affect peroxisome biogenesis and methylotrophic growth
Two interacting AAA ATPases, Pex1p and Pex6p, are indispensable for peroxisome biogenesis in different organisms. Mutations affecting corresponding genes are the most common cause of the peroxisome biogenesis disorders in humans. By UV mutagenesis of the Hansenula polymorpha pex6 mutant, deficient in peroxisome biogenesis, we isolated a conditional cold-sensitive strain with restored ability to grow in methanol medium at 37degreesC but not at 28degreesC. Sequencing of the pex6 allele revealed a point mutation in the first AAA module of the PEX6 gene that leads to substitution of a conserved amino acid residue (G737E). An additional intragenic mutation identified in the cold-sensitive pex6 allele leads to a conserved amino acid substitution in the second AAA domain (R1000G). Electron microscopic analysis revealed restored peroxisomes in methanol-induced cold-sensitive pex6 cells at both permissive and restrictive temperatures. If separated, the secondary mutation did not affect methylotrophic growth. Our data suggest that H. polymorpha Pex6p may have a complex function in peroxisome biogenesis in which identified amino acid residues are involved. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Microbiological Societies
Insights into the prevalence and underlying causes of clonal variation through transcriptomic analysis in Pichia pastoris
SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated Beclin1 phosphorylation
Curcumin synergizes with 5-fluorouracil by impairing AMPK/ULK1-dependent autophagy, AKT activity and enhancing apoptosis in colon cancer cells with tumor growth inhibition in xenograft mice
TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKβ/VPS34 pathway
Multi-localized proteins: the peroxisome-mitochondria connection
This is the author accepted manuscript. The final version is available from Springer via the link in this recordPeroxisomes and mitochondria are dynamic, multifunctional organelles that play pivotal cooperative roles in the metabolism of cellular lipids and reactive oxygen species. Their functional interplay, the “peroxisome-mitochondria connection”, also includes cooperation in anti-viral signalling and defence, as well as coordinated biogenesis by sharing key division proteins. In this review, we focus on multi-localised proteins which are shared by peroxisomes and mitochondria in mammals. We first outline the targeting and sharing of matrix proteins which are involved in metabolic cooperation. Next, we discuss shared components of peroxisomal and mitochondrial dynamics and division, and we present novel insights into the dual targeting of tail-anchored membrane proteins. Finally, we provide an overview of what is currently known about the role of shared membrane proteins in disease. What emerges is that sharing of proteins between these two organelles plays a key role in their cooperative functions which, based on new findings, may be more extensive than originally envisaged. Gaining a better insight into organelle interplay and the targeting of shared proteins is pivotal to understanding how organelle cooperation contributes to human health and disease.This work was supported by the Biotechnology and Biological Sciences Research Council (BB/K006231/1, BB/N01541X/1 to M.S.). M.I. is supported by the German Research Foundation (DFG 397476530) and MEAMEDMA Anschubförderung, Medical Faculty Mannheim, University of Heidelberg. J.P. is supported by CLES, University of Exeter