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Article ; Online: Autophagy in unicellular eukaryotes.

Kiel, Jan A K W

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

2010 Volume 365, Issue 1541, Page(s) 819–830

Abstract: Cells need a constant supply of precursors to enable the production of macromolecules to sustain growth and survival. Unlike metazoans, unicellular eukaryotes depend exclusively on the extracellular medium for this supply. When environmental nutrients ... ...

Abstract	Cells need a constant supply of precursors to enable the production of macromolecules to sustain growth and survival. Unlike metazoans, unicellular eukaryotes depend exclusively on the extracellular medium for this supply. When environmental nutrients become depleted, existing cytoplasmic components will be catabolized by (macro)autophagy in order to re-use building blocks and to support ATP production. In many cases, autophagy takes care of cellular housekeeping to sustain cellular viability. Autophagy encompasses a multitude of related and often highly specific processes that are implicated in both biogenetic and catabolic processes. Recent data indicate that in some unicellular eukaryotes that undergo profound differentiation during their life cycle (e.g. kinetoplastid parasites and amoebes), autophagy is essential for the developmental change that allows the cell to adapt to a new host or form spores. This review summarizes the knowledge on the molecular mechanisms of autophagy as well as the cytoplasm-to-vacuole-targeting pathway, pexophagy, mitophagy, ER-phagy, ribophagy and piecemeal microautophagy of the nucleus, all highly selective forms of autophagy that have first been uncovered in yeast species. Additionally, a detailed analysis will be presented on the state of knowledge on autophagy in non-yeast unicellular eukaryotes with emphasis on the role of this process in differentiation.
MeSH term(s)	Autophagy/physiology ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Dictyostelium/cytology ; Dictyostelium/genetics ; Dictyostelium/growth & development ; Dictyostelium/physiology ; Endoplasmic Reticulum/metabolism ; Entamoeba/cytology ; Entamoeba/genetics ; Entamoeba/growth & development ; Entamoeba/physiology ; Eukaryota/cytology ; Eukaryota/genetics ; Eukaryota/growth & development ; Eukaryota/physiology ; Leishmania/cytology ; Leishmania/genetics ; Leishmania/growth & development ; Leishmania/physiology ; Models, Biological ; Peroxisomes/metabolism ; Phagosomes/metabolism ; Ribosomes/metabolism ; Saccharomyces cerevisiae/cytology ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/growth & development ; Saccharomyces cerevisiae/physiology ; Saccharomyces cerevisiae Proteins/metabolism ; Trypanosoma/cytology ; Trypanosoma/genetics ; Trypanosoma/growth & development ; Trypanosoma/physiology ; Vacuoles/metabolism
Chemical Substances	Saccharomyces cerevisiae Proteins
Language	English
Publishing date	2010-02-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	208382-6
ISSN	1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
ISSN (online)	1471-2970
ISSN	0080-4622 ; 0264-3839 ; 0962-8436
DOI	10.1098/rstb.2009.0237
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Article ; Online: The role of macroautophagy in development of filamentous fungi.

Bartoszewska, Magdalena / Kiel, Jan A K W

Antioxidants & redox signaling

2011 Volume 14, Issue 11, Page(s) 2271–2287

Abstract: Autophagy (macroautophagy) is a bulk degradative pathway by which cytoplasmic components are delivered to the vacuole for recycling. This process is conserved from yeast to human, where it is implicated in cancer and neurodegenerative diseases. During ... ...

Abstract	Autophagy (macroautophagy) is a bulk degradative pathway by which cytoplasmic components are delivered to the vacuole for recycling. This process is conserved from yeast to human, where it is implicated in cancer and neurodegenerative diseases. During the last decade, many ATG genes involved in autophagy have been identified, initially in Saccharomyces cerevisiae. This review summarizes the knowledge on the molecular mechanisms of autophagy using yeast as model system. Although many of the core components involved in autophagy are conserved from yeast to human, there are, nevertheless, significant differences between these organisms, for example, during autophagy initiation. Autophagy also plays an essential role in filamentous fungi especially during differentiation. Remarkably, in these species autophagy may reflect features of both yeast and mammals. This is exemplified by the finding that filamentous fungi lack the S. cerevisiae clade-specific Atg31 protein, but contain Atg101, which is absent in this clade. A reappraisal of genome data further suggests that, similar to yeast and mammals, filamentous fungi probably also contain two distinct phosphatidylinositol 3-kinase complexes. This review also summarizes the state of knowledge on the role of autophagy in filamentous fungi during differentiation, such as pathogenic development, programmed cell death during heteroincompatibility, and spore formation.
MeSH term(s)	Amino Acid Sequence ; Animals ; Autophagy ; Fungi/growth & development ; Fungi/physiology ; Host-Pathogen Interactions ; Humans ; Molecular Sequence Data ; Mycoses/metabolism ; Mycoses/microbiology ; Oryza/microbiology ; Phosphatidylinositol 3-Kinases/metabolism ; Plant Diseases/microbiology ; Saccharomyces cerevisiae Proteins/metabolism ; Sequence Alignment
Chemical Substances	Saccharomyces cerevisiae Proteins ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
Language	English
Publishing date	2011-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2010.3528
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Article ; Online: Proteins involved in microbody biogenesis and degradation in Aspergillus nidulans.

Kiel, Jan A K W / van der Klei, Ida J

Fungal genetics and biology : FG & B

2009 Volume 46 Suppl 1, Page(s) S62–71

Abstract: Fungal microbodies (peroxisomes) are inducible organelles that proliferate in response to nutritional cues. Proteins involved in peroxisome biogenesis/proliferation are designated peroxins and are encoded by PEX genes. An autophagy-related process, ... ...

Abstract	Fungal microbodies (peroxisomes) are inducible organelles that proliferate in response to nutritional cues. Proteins involved in peroxisome biogenesis/proliferation are designated peroxins and are encoded by PEX genes. An autophagy-related process, termed pexophagy, is responsible for the selective removal of peroxisomes from the cell. Several genes involved in pexophagy are also required for autophagy and are collectively known as ATG genes. We have re-analysed the Aspergillus nidulans genome for the presence of PEX and ATG genes and have identified a number of previously missed genes. Also, we manually determined the correct intron positions in each identified gene. The data show that in A. nidulans and related fungi the basic set of genes involved in peroxisome biogenesis or degradation are conserved. However, both processes have features that more closely resemble organelle formation/degradation in mammals rather than yeast. Thus, filamentous fungi like A. nidulans are ideal model systems for peroxisome homeostasis in man.
MeSH term(s)	Aspergillus nidulans/genetics ; Aspergillus nidulans/metabolism ; Conserved Sequence ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Introns ; Microbodies/metabolism
Chemical Substances	Fungal Proteins
Language	English
Publishing date	2009-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1319820-8
ISSN	1096-0937 ; 1087-1845 ; 0147-5975
ISSN (online)	1096-0937
ISSN	1087-1845 ; 0147-5975
DOI	10.1016/j.fgb.2008.07.009
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Article ; Conference proceedings: The 4th Hansenula polymorpha Worldwide Network Conference, Haren (The Netherlands), 3-5 September 2006.

Kiel, Jan A K W / Otzen, Marleen

FEMS yeast research

2007 Volume 7, Issue 1, Page(s) 167–171

MeSH term(s)	Biotechnology/methods ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Gene Expression Regulation, Fungal ; Peroxisomes/metabolism ; Pichia/genetics ; Pichia/growth & development ; Pichia/metabolism ; Pichia/physiology
Chemical Substances	Fungal Proteins
Language	English
Publishing date	2007-01
Publishing country	England
Document type	Congresses
ZDB-ID	2036775-2
ISSN	1567-1364 ; 1567-1356
ISSN (online)	1567-1364
ISSN	1567-1356
DOI	10.1111/j.1567-1364.2006.00200.x
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Article ; Online: Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.

Sarnowski, Chloé / Chen, Han / Biggs, Mary L / Wassertheil-Smoller, Sylvia / Bressler, Jan / Irvin, Marguerite R / Ryan, Kathleen A / Karasik, David / Arnett, Donna K / Cupples, L Adrienne / Fardo, David W / Gogarten, Stephanie M / Heavner, Benjamin D / Jain, Deepti / Kang, Hyun Min / Kooperberg, Charles / Mainous, Arch G / Mitchell, Braxton D / Morrison, Alanna C /

O'Connell, Jeffrey R / Psaty, Bruce M / Rice, Kenneth / Smith, Albert V / Vasan, Ramachandran S / Windham, B Gwen / Kiel, Douglas P / Murabito, Joanne M / Lunetta, Kathryn L

PloS one

2021 Volume 16, Issue 7, Page(s) e0253611

Abstract: Handgrip strength is a widely used measure of muscle strength and a predictor of a range of morbidities including cardiovascular diseases and all-cause mortality. Previous genome-wide association studies of handgrip strength have focused on common ... ...

Abstract	Handgrip strength is a widely used measure of muscle strength and a predictor of a range of morbidities including cardiovascular diseases and all-cause mortality. Previous genome-wide association studies of handgrip strength have focused on common variants primarily in persons of European descent. We aimed to identify rare and ancestry-specific genetic variants associated with handgrip strength by conducting whole-genome sequence association analyses using 13,552 participants from six studies representing diverse population groups from the Trans-Omics in Precision Medicine (TOPMed) Program. By leveraging multiple handgrip strength measures performed in study participants over time, we increased our effective sample size by 7-12%. Single-variant analyses identified ten handgrip strength loci among African-Americans: four rare variants, five low-frequency variants, and one common variant. One significant and four suggestive genes were identified associated with handgrip strength when aggregating rare and functional variants; all associations were ancestry-specific. We additionally leveraged the different ancestries available in the UK Biobank to further explore the ancestry-specific association signals from the single-variant association analyses. In conclusion, our study identified 11 new loci associated with handgrip strength with rare and/or ancestry-specific genetic variations, highlighting the added value of whole-genome sequencing in diverse samples. Several of the associations identified using single-variant or aggregate analyses lie in genes with a function relevant to the brain or muscle or were reported to be associated with muscle or age-related traits. Further studies in samples with sequence data and diverse ancestries are needed to confirm these findings.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Hand Strength/physiology ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Precision Medicine/statistics & numerical data ; Racial Groups/genetics ; Racial Groups/statistics & numerical data ; Whole Genome Sequencing/statistics & numerical data
Language	English
Publishing date	2021-07-02
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0253611
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Article: Proteins involved in microbody biogenesis and degradation in Aspergillus nidulans

Kiel, Jan A.K.W / Klei, Ida J. van der

Fungal genetics and biology : FG & B. 2009 Mar., v. 46, issue 1, suppl. 1

2009

Keywords	Aspergillus nidulellus ; peroxisomes ; fungal proteins ; organelles ; fungus physiology ; nutrient availability ; genes ; microbial genetics ; genome ; genomics ; introns ; sequence analysis ; sequence alignment ; species differences
Language	English
Dates of publication	2009-03
Size	p. S62-S71.
Document type	Article
Note	In the special issue: Aspergillus genomics and beyond / edited by Jaap Visser, Jennifer Russo Wortman, Albert J.J. van Ooyen, Scott Baker, Jens Nielsen and Cees van den Hondel.
ZDB-ID	1319820-8
ISSN	1096-0937 ; 1087-1845 ; 0147-5975
ISSN (online)	1096-0937
ISSN	1087-1845 ; 0147-5975
DOI	10.1016/j.fgb.2008.07.009
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Article ; Online: Membrane curvature during peroxisome fission requires Pex11.

Opaliński, Łukasz / Kiel, Jan A K W / Williams, Chris / Veenhuis, Marten / van der Klei, Ida J

The EMBO journal

2010 Volume 30, Issue 1, Page(s) 5–16

Abstract: Pex11 is a key player in peroxisome proliferation, but the molecular mechanisms of its function are still unknown. Here, we show that Pex11 contains a conserved sequence at the N-terminus that can adopt the structure of an amphipathic helix. Using ... ...

Abstract	Pex11 is a key player in peroxisome proliferation, but the molecular mechanisms of its function are still unknown. Here, we show that Pex11 contains a conserved sequence at the N-terminus that can adopt the structure of an amphipathic helix. Using Penicillium chrysogenum Pex11, we show that this amphipathic helix, termed Pex11-Amph, associates with liposomes in vitro. This interaction is especially evident when negatively charged liposomes are used with a phospholipid content resembling that of peroxisomal membranes. Binding of Pex11-Amph to negatively charged membrane vesicles resulted in strong tubulation. This tubulation of vesicles was also observed when the entire soluble N-terminal domain of Pex11 was used. Using mutant peptides, we demonstrate that maintaining the amphipathic properties of Pex11-Amph in conjunction with retaining its α-helical structure are crucial for its function. We show that the membrane remodelling capacity of the amphipathic helix in Pex11 is conserved from yeast to man. Finally, we demonstrate that mutations abolishing the membrane remodelling activity of the Pex11-Amph domain also hamper the function of full-length Pex11 in peroxisome fission in vivo.
MeSH term(s)	Amino Acid Sequence ; Fungal Proteins/chemistry ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Humans ; Intracellular Membranes/chemistry ; Intracellular Membranes/metabolism ; Liposomes/chemistry ; Liposomes/metabolism ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Molecular Sequence Data ; Mutation ; Penicillium chrysogenum/chemistry ; Penicillium chrysogenum/genetics ; Penicillium chrysogenum/metabolism ; Peroxisomes/chemistry ; Peroxisomes/metabolism ; Phospholipids/chemistry ; Phospholipids/metabolism ; Protein Structure, Secondary ; Sequence Alignment
Chemical Substances	Fungal Proteins ; Liposomes ; Membrane Proteins ; Phospholipids
Language	English
Publishing date	2010-11-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.1038/emboj.2010.299
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Article: The Hansenula polymorpha PDD7 gene is essential for macropexophagy and microautophagy.

Komduur, Janet A / Veenhuis, Marten / Kiel, Jan A K W

FEMS yeast research

2003 Volume 3, Issue 1, Page(s) 27–34

Abstract: Hansenula polymorpha PDD genes are involved in the selective degradation of peroxisomes via macropexophagy. We have isolated various novel pdd mutants by a gene-tagging method. Here we describe the isolation and characterisation of PDD7, which encodes a ... ...

Abstract	Hansenula polymorpha PDD genes are involved in the selective degradation of peroxisomes via macropexophagy. We have isolated various novel pdd mutants by a gene-tagging method. Here we describe the isolation and characterisation of PDD7, which encodes a protein with high sequence similarity (40% identity) to Saccharomyces cerevisiae Apg1p/Aut3p, previously described to be involved in random autophagy and the cytoplasm-to-vacuole targeting pathway. Our data indicate that HpPdd7p is essential for two processes that degrade peroxisomes, namely the highly selective process of macropexophagy and microautophagy, which occurs in H. polymorpha upon nitrogen starvation.
MeSH term(s)	Amino Acid Sequence ; Autophagy/genetics ; Biological Transport ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Fungal Proteins/physiology ; Genome, Fungal ; Molecular Sequence Data ; Peroxisomes/metabolism ; Pichia/enzymology ; Pichia/genetics ; Pichia/metabolism ; Pichia/ultrastructure ; Sequence Homology, Amino Acid ; Vacuoles/enzymology ; Vacuoles/ultrastructure
Chemical Substances	Fungal Proteins
Language	English
Publishing date	2003-01-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2036775-2
ISSN	1567-1364 ; 1567-1356
ISSN (online)	1567-1364
ISSN	1567-1356
DOI	10.1016/s1567-1356(02)00135-6
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Article: Selective degradation of peroxisomes in yeasts.

Bellu, Anna Rita / Kiel, Jan A K W

Microscopy research and technique

2003 Volume 61, Issue 2, Page(s) 161–170

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Biological Transport ; Fungal Proteins/metabolism ; Gene Expression Regulation, Fungal ; Membrane Proteins/metabolism ; Methanol/metabolism ; Peroxisomes/metabolism ; Signal Transduction ; Vacuoles/metabolism ; Yeasts/growth & development ; Yeasts/metabolism
Chemical Substances	Fungal Proteins ; Membrane Proteins ; Methanol (Y4S76JWI15)
Language	English
Publishing date	2003-06-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1099714-3
ISSN	1097-0029 ; 1059-910X
ISSN (online)	1097-0029
ISSN	1059-910X
DOI	10.1002/jemt.10325
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Article ; Online: Novel genetic tools for Hansenula polymorpha.

Saraya, Ruchi / Krikken, Arjen M / Kiel, Jan A K W / Baerends, Richard J S / Veenhuis, Marten / van der Klei, Ida J

FEMS yeast research

2012 Volume 12, Issue 3, Page(s) 271–278

Abstract: Hansenula polymorpha is an important yeast in industrial biotechnology. In addition, it is extensively used in fundamental research devoted to unravel the principles of peroxisome biology and nitrate assimilation. Here we present an overview of key ... ...

Abstract	Hansenula polymorpha is an important yeast in industrial biotechnology. In addition, it is extensively used in fundamental research devoted to unravel the principles of peroxisome biology and nitrate assimilation. Here we present an overview of key components of the genetic toolbox for H. polymorpha. In addition, we present new selection markers that we recently implemented in H. polymorpha. We describe novel strategies for the efficient creation of targeted gene deletions and integrations in H. polymorpha. For this, we generated a yku80 mutant, deficient in non-homologous end joining, resulting in strongly enhanced efficiency of gene targeting relative to the parental strain. Finally, we show the implementation of Gateway technology and a single-step PCR strategy to create deletions in H. polymorpha.
MeSH term(s)	Biotechnology/methods ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Gene Deletion ; Gene Expression ; Genetic Engineering/methods ; Genetic Vectors/genetics ; Pichia/genetics ; Plasmids/genetics ; Polymerase Chain Reaction ; Recombination, Genetic
Chemical Substances	Fungal Proteins
Language	English
Publishing date	2012-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036775-2
ISSN	1567-1364 ; 1567-1356
ISSN (online)	1567-1364
ISSN	1567-1356
DOI	10.1111/j.1567-1364.2011.00772.x
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