Publicação
Characterization of dysferlin domain-containing peroxins in lipid droplet biogenesis
| Resumo: | Lipid droplets (LDs) are ubiquitous organelles of crucial importance in cell biology, understanding of human diseases and biotechnology because they are cellular reservoirs of neutral lipids for energy production or membrane synthesis and act as hubs for metabolic processes. Despite continued efforts, the molecular mechanisms of LD biogenesis are not completely understood. Recent reports indicated that LD biogenesis and formation of pre-peroxisomal vesicles, which are involved in peroxisomes biogenesis, occur at the same endoplasmic reticulum (ER) sites, suggesting that these sites are specific and distinct from bulk ER. Moreover, the ER budding of both these structurally unrelated organelles involves cooperation between Seipin and Pex30p, since, in absence of these proteins, budding of these organelles is inhibited. However, the molecular mechanisms regarding this cooperation remain elusive. Since no peroxin of pex30p family - dysferlin domain-containing peroxin family - has been described before as involved in LD biogenesis, it is unclear how Pex30p is localised to the LDs in absence of the Seipin complex. It is also unknown what is the central function of Pex30p in LD budding and whether other peroxins of the same family of Pex30p are also involved in LD biogenesis. In the present work, we show that all dysferlin domain-containing peroxins accumulate at LDs in absence of the Seipin complex. However, Pex28p, Pex29p, Pex31p and Pex32p do not exert the same function as Pex30p in LD budding. Nevertheless, we demonstrate that some of these peroxins seem to regulate and target Pex30p to other organelles in specific metabolic conditions. We also found the novel role of dysferlin domain as essential for Pex30p localisation at the LDs and this propriety is conserved among some of the dysferlin domain-containing peroxins. We propose that the dysferlin domain-containing peroxins associate in a protein complex and act in concert to define their localisation and function in response to the metabolic conditions. Such a complex may then regulate intracellular communication among several organelles in which dysferlin domain-containing peroxins play several functions, contributing to coordinate organelle biogenesis and, consequently, cell homeostasis. |
|---|---|
| Autores principais: | Ferreira, Joana Patrícia Veríssimo |
| Assunto: | LD biogenesis LD budding Saccharomyces cerevisiae Seipin Pex30 Peroxins Dysferlin domain Reticulon-homology domain Biogenese de PLs Budding de PLs Peroxinas Disferlina Domínio reticulon-homology |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Lipid droplets (LDs) are ubiquitous organelles of crucial importance in cell biology, understanding of human diseases and biotechnology because they are cellular reservoirs of neutral lipids for energy production or membrane synthesis and act as hubs for metabolic processes. Despite continued efforts, the molecular mechanisms of LD biogenesis are not completely understood. Recent reports indicated that LD biogenesis and formation of pre-peroxisomal vesicles, which are involved in peroxisomes biogenesis, occur at the same endoplasmic reticulum (ER) sites, suggesting that these sites are specific and distinct from bulk ER. Moreover, the ER budding of both these structurally unrelated organelles involves cooperation between Seipin and Pex30p, since, in absence of these proteins, budding of these organelles is inhibited. However, the molecular mechanisms regarding this cooperation remain elusive. Since no peroxin of pex30p family - dysferlin domain-containing peroxin family - has been described before as involved in LD biogenesis, it is unclear how Pex30p is localised to the LDs in absence of the Seipin complex. It is also unknown what is the central function of Pex30p in LD budding and whether other peroxins of the same family of Pex30p are also involved in LD biogenesis. In the present work, we show that all dysferlin domain-containing peroxins accumulate at LDs in absence of the Seipin complex. However, Pex28p, Pex29p, Pex31p and Pex32p do not exert the same function as Pex30p in LD budding. Nevertheless, we demonstrate that some of these peroxins seem to regulate and target Pex30p to other organelles in specific metabolic conditions. We also found the novel role of dysferlin domain as essential for Pex30p localisation at the LDs and this propriety is conserved among some of the dysferlin domain-containing peroxins. We propose that the dysferlin domain-containing peroxins associate in a protein complex and act in concert to define their localisation and function in response to the metabolic conditions. Such a complex may then regulate intracellular communication among several organelles in which dysferlin domain-containing peroxins play several functions, contributing to coordinate organelle biogenesis and, consequently, cell homeostasis. |
|---|