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

Special Issue on “Ubiquitin and Autophagy”

The Special Issue of Cells on “Ubiquitin and Autophagy” is a tribute to the multifaceted role of ubiquitin and autophagic ubiquitin-like (UBL) proteins in the autophagy-related (ATG) pathways [...]</jats:p

Autophagy of glycogen is non-selective in Komagataella phaffii

Glycogen is an important reserve polysaccharide from bacteria to human. It is organized in glycogen granules that also contain several proteins involved in their metabolism. Glycogen granules can be mobilized in mammalian lysosomes and yeast vacuoles. They are delivered to these organelles by macroautophagy (hereafter autophagy). However, whether this is a selective or a non-selective process remains a matter of debate. It was proposed to be selective and called “glycophagy” (for selective autophagy of glycogen) in mouse liver. However, the evidence of this selectivity is lacking in other glycogen-rich organs, such as the heart and skeletal muscle, which both are heavily impacted by the aberrant lysosomal accumulation of glycogen in Pompe disease. We recently developed the Komagataella phaffii yeast as a simple model to study the relationship of glycogen and autophagy. Using this model, we showed that cytosolic glycogen granules are delivered to the vacuole by non-selective autophagy, at least during nitrogen starvation. We speculate that this type of autophagy might be responsible for the lysosomal glycogen turnover in non-hepatic mammalian tissues.Abbreviations GFP, green fluorescent protein

Special Issue on “Ubiquitin and Autophagy”

The Special Issue of Cells on &ldquo;Ubiquitin and Autophagy&rdquo; is a tribute to the multifaceted role of ubiquitin and autophagic ubiquitin-like (UBL) proteins in the autophagy-related (ATG) pathways [...

The Molecular Interplay between Human Coronaviruses and Autophagy

Coronavirus disease 2019 (COVID-19), caused by a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has instantaneously emerged as a worldwide pandemic. However, humans encountered other coronaviruses in the past, and they caused a broad range of symptoms, from mild to life-threatening, depending on the virus and immunocompetence of the host. Most human coronaviruses interact with the proteins and/or double-membrane vesicles of autophagy, the membrane trafficking pathway that degrades and recycles the intracellular protein aggregates, organelles, and pathogens, including viruses. However, coronaviruses often neutralize and hijack this pathway to complete their life cycle. In this review, we discuss the interactions of human coronaviruses and autophagy, including recent data from SARS-CoV-2-related studies. Some of these interactions (for example, viral block of the autophagosome–lysosome fusion), while being conserved across multiple coronaviruses, are accomplished via different molecular mechanisms. Therefore, it is important to understand the molecular interplay between human coronaviruses and autophagy for developing efficient therapies against coronaviral diseases.</jats:p

The Molecular Interplay between Human Coronaviruses and Autophagy

Coronavirus disease 2019 (COVID-19), caused by a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has instantaneously emerged as a worldwide pandemic. However, humans encountered other coronaviruses in the past, and they caused a broad range of symptoms, from mild to life-threatening, depending on the virus and immunocompetence of the host. Most human coronaviruses interact with the proteins and/or double-membrane vesicles of autophagy, the membrane trafficking pathway that degrades and recycles the intracellular protein aggregates, organelles, and pathogens, including viruses. However, coronaviruses often neutralize and hijack this pathway to complete their life cycle. In this review, we discuss the interactions of human coronaviruses and autophagy, including recent data from SARS-CoV-2-related studies. Some of these interactions (for example, viral block of the autophagosome–lysosome fusion), while being conserved across multiple coronaviruses, are accomplished via different molecular mechanisms. Therefore, it is important to understand the molecular interplay between human coronaviruses and autophagy for developing efficient therapies against coronaviral diseases