Assessing Organismal Aging in the Filamentous Fungus Podospora anserina

Osiewacz, Heinz; Hamann, Andréa; Zintel, Sandra

doi:10.1007/978-1-62703-239-1_29

Cited by 49 publications

(89 citation statements)

References 25 publications

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“…The first molecular evidence for age-related reorganization of mtDNA is derived from the fungal ageing model Podospora anserina [23]. This fungus is characterized by a limited lifespan and a senescence syndrome [24].…”

Section: Mutations In Mtdna In Relation To Ageing and Diseasementioning

confidence: 99%

Control of mitochondrial integrity in ageing and disease

Szklarczyk

Nooteboom

Osiewacz

2014

Phil. Trans. R. Soc. B

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Various molecular and cellular pathways are active in eukaryotes to control the quality and integrity of mitochondria. These pathways are involved in keeping a ‘healthy’ population of this essential organelle during the lifetime of the organism. Quality control (QC) systems counteract processes that lead to organellar dysfunction manifesting as degenerative diseases and ageing. We discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA repair and reorganization, regeneration of oxidized amino acids, refolding and degradation of severely damaged proteins, degradation of whole mitochondria by mitophagy and finally programmed cell death. The control of the integrity of mtDNA and regulation of its expression is essential to remodel single proteins as well as mitochondrial complexes that determine mitochondrial functions. The redundancy of components, such as proteases, and the hierarchies of the QC raise questions about crosstalk between systems and their precise regulation. The understanding of the underlying mechanisms on the genomic, proteomic, organellar and cellular levels holds the key for the development of interventions for mitochondrial dysfunctions, degenerative processes, ageing and age-related diseases resulting from impairments of mitochondria.

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Section: Mutations In Mtdna In Relation To Ageing and Diseasementioning

confidence: 99%

Control of mitochondrial integrity in ageing and disease

Szklarczyk

Nooteboom

Osiewacz

2014

Phil. Trans. R. Soc. B

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“…In order to use optimal and reproducible growth conditions, we performed the experiments on the widely used semi-synthetic M2 medium (Knuppertz et al, 2014;Osiewacz et al, 2013). Since PaSOD3 is an enzyme utilizing manganese as a metal cofactor, we investigated the impact of this trace metal on PaSod3 overexpressors and found that the adverse phenotype is reversed by the addition of 80 μM MnSO 4 to the M2 medium.…”

Section: Discussionmentioning

confidence: 99%

“…All transgenic strains are in the genetic background of the wild-type strain 's'. Strains were grown on standard cornmeal agar (BMM) at 27°C under constant light (Esser, 1974;Osiewacz et al, 2013). For germination of spores BMM with 60 mM ammonium acetate was used and incubated at 27°C in the dark for three days.…”

Section: Cultivation Of P Anserina Strainsmentioning

confidence: 99%

Manganese rescues adverse effects on lifespan and development in Podospora anserina challenged by excess hydrogen peroxide

Grimm

Osiewacz

2015

Experimental Gerontology

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“…For PaMCA1-inducing growth conditions, M2 medium contained 1.5 mM H 2 O 2 . Germination of ascospores was performed on agar biomalt maize (BMM) complete medium supplemented with 60 mM ammonium acetate and incubated at 27°C for 2 days in the dark (46). RNA isolation and cDNA synthesis.…”

Section: Methodsmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerase Is a Substrate Recognized by Two Metacaspases of Podospora anserina

Strobel

Osiewacz

2013

Eukaryot Cell

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The two metacaspases MCA1 and MCA2 of the fungal aging model organism Podospora anserina (PaMCA1 and PaMCA2, respectively) have previously been demonstrated to be involved in the control of programmed cell death (PCD) and life span. In order to identify specific pathways and components which are controlled by the activity of these enzymes, we set out to characterize them further. Heterologous overexpression in Escherichia coli of the two metacaspase genes resulted in the production of proteins which aggregate and form inclusion bodies from which the active protein has been recovered via refolding in appropriate buffers. The renaturated proteins are characterized by an arginine-specific activity and are active in caspase-like self-maturation leading to the generation of characteristic small protein fragments. Both activities are dependent on the presence of calcium. Incubation of the two metacaspases with recombinant poly(ADP-ribose) polymerase (PARP), a known substrate of mammalian caspases, led to the identification of PARP as a substrate of the two P. anserina proteases. Using double mutants in which P. anserina Parp (PaParp) is overexpressed and PaMca1 is either overexpressed or deleted, we provide evidence for in vivo degradation of PaPARP by PaMCA1. These results support the idea that the substrate profiles of caspases and metacaspases are at least partially overlapping. Moreover, they link PCD and DNA maintenance in the complex network of molecular pathways involved in aging and life span control.A poptosis is a type of programmed cell death (PCD) that is fundamental in removing unneeded cells from the body during development of multicellular organisms. In addition, in mammals, apoptosis plays a key role in removing severely damaged cells which are at risk of transforming into cancer cells. In unicellular and multicellular lower eukaryotes, like the yeast Saccharomyces cerevisiae, or in filamentous fungi, the role of PCD is less clear and leads to death of the whole organism or parts of it. Previously, it has been suggested that under natural conditions under which individuals compete for the available nutrients, PCD guarantees the conservation of the species via providing nutrients and other factors for survival of younger cells (1, 2).Although differing in complexity, basic components and reactions associated with PCD are known to be conserved from lower eukaryotes to mammals. For instance, DNA fragmentation, the release of apoptotic factors from mitochondria, and the activation of specific cysteine proteases are hallmarks of apoptosis in all eukaryotic systems (3, 4). In fungi, plants, and protozoa, metacaspases were identified as sequence homologs of mammalian caspases (5). Caspases and metacaspases share structural similarities such as a common caspase hemoglobinase fold and conserved catalytic cysteine and histidine residues. Metacaspases can be subdivided into type I and type II analogs to mammalian initiator and effector caspases, respectively. The characteristic amino-terminal domain of type I met...

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Assessing Organismal Aging in the Filamentous Fungus Podospora anserina

Cited by 49 publications

References 25 publications

Control of mitochondrial integrity in ageing and disease

Control of mitochondrial integrity in ageing and disease

Manganese rescues adverse effects on lifespan and development in Podospora anserina challenged by excess hydrogen peroxide

Poly(ADP-Ribose) Polymerase Is a Substrate Recognized by Two Metacaspases of Podospora anserina

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