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Cellular Homeostasis in Fungi: Impact on the Aging Process

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Aging Research in Yeast

Part of the book series: Subcellular Biochemistry ((SCBI,volume 57))

Abstract

Cellular quality control pathways are needed for maintaining the biological function of organisms. If these pathways become compromised, the results are usually highly detrimental. Functional impairments of cell components can lead to diseases and in extreme cases to organismal death. Dysfunction of cells can be induced by a number of toxic by-products that are formed during metabolic activity, like reactive oxygen and nitrogen species, for example. A key source of reactive oxygen species (ROS) are the organelles of oxidative phosphorylation, mitochondria. Therefore mitochondrial function is also directly affected by ROS, especially if there is a compromised ROS-scavenging capacity. Biological systems therefore depend on several lines of defence to counteract the toxic effects of ROS and other damaging agents. The first level is active at the molecular level and consists of various proteases that bind and degrade abnormally modified and / or aggregated mitochondrial proteins. The second level is concerned with maintaining the quality of whole mitochondria. Among the pathways of this level are mitochondrial dynamics and autophagy (mitophagy). Mitochondrial dynamics describes the time-dependent fusion and fission of mitochondria. It is argued that this kind of organellar dynamics has the power to restore the function of impaired organelles by content mixing with intact organelles. If the first and second lines of defence against damage fail and mitochondria become damaged too severely, there is the option to remove affected cells before they can elicit more damage to their surrounding environment by apoptosis. This form of programmed cell death is strictly regulated by a complex network of interacting components and can be divided into mitochondria-dependent and mitochondria-independent modes of action. In this review we give an overview on various biological quality control systems in fungi (yeasts and filamentous fungi) with an emphasis on autophagy (mitophagy) and apoptosis and how these pathways allow fungal organisms to maintain a balanced cellular homeostasis.

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Abbreviations

AIF:

apoptosis inducing factor

Amid:

AIF-homologous mitochondrion-associated inducer of death

COX:

cytochrome c oxidase

CvT:

cytoplasm-to-vacuole targeting

ER:

endoplasmic reticulum

GFP:

green fluorescent protein

MIPA:

micropexophagic membrane apparatus

PAS:

pre-autophagosomal structure

RNAi:

RNA interference

ROS:

reactive oxygen species

TOR:

target of rapamycin

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Authors and Affiliations

  1. Faculty of Biosciences, Institute of Molecular Biosciences and Cluster of Excellence Macromolecular Complexes, Johann Wolfgang Goethe University, 60438, Frankfurt/Main, Germany

    Christian Q. Scheckhuber, Andrea Hamann, Diana Brust & Heinz D. Osiewacz

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  1. Christian Q. Scheckhuber
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  2. Andrea Hamann
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  3. Diana Brust
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  4. Heinz D. Osiewacz
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Correspondence to Heinz D. Osiewacz .

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Editors and Affiliations

  1. , Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Michael Breitenbach

  2. , Tulane Center for Aging and Department o, Tulane University Health Sciences Center, Tulane Avenue SL-12 1430, New Orleans, 70112, Louisiana, USA

    S. Michal Jazwinski

  3. , Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Peter Laun

Appendix

Appendix

A short description of recent important papers related to the topic of this chapter.

Although the understanding of the mechanisms regulating mitophagy has progressed in the last years, there remain still some important questions, e.g. how the molecular autophagy machinery is able to detect energetically compromised mitochondria . A possible key factor in this regard could be the protein Atg32 which has been recently identified in two independent screens for genes involved in S. cerevisiae mitophagy (Okamoto et al. 2009; Kanki et al. 2010). ATG32 was shown to be a protein residing in the outer mitochondrial membrane. Interestingly, ATG32 is neither needed for bulk autophagy nor pexophagy but is essential for the removal of mitochondria when yeast cells are grown under respiratory conditions (Kanki et al. 2009). So far, it is not clear whether ATG32 may act as a signal for compromised mitochondria, because Atg32 deletion mutants show no obvious mitochondrial defects. Therefore it is certainly possible that there are further, hitherto unknown factors that might act as signals or effectors for maintaining quality control of mitochondria by mitophagy .

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Scheckhuber, C.Q., Hamann, A., Brust, D., Osiewacz, H.D. (2011). Cellular Homeostasis in Fungi: Impact on the Aging Process. In: Breitenbach, M., Jazwinski, S., Laun, P. (eds) Aging Research in Yeast. Subcellular Biochemistry, vol 57. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2561-4_11

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