Lifespan Increase of Podospora anserina by Oleic Acid Is Linked to Alterations in Energy Metabolism, Membrane Trafficking and Autophagy

Abstract

The maintenance of cellular homeostasis over time is essential to avoid the degeneration of biological systems leading to aging and disease. Several interconnected pathways are active in this kind of quality control. One of them is autophagy, the vacuolar degradation of cellular components. The absence of the sorting nexin PaATG24 (SNX4 in other organisms) has been demonstrated to result in impairments in different types of autophagy and lead to a shortened lifespan. In addition, the growth rate and the size of vacuoles are strongly reduced. Here, we report how an oleic acid diet leads to longevity of the wild type and a PaAtg24 deletion mutant (ΔPaAtg24). The lifespan extension is linked to altered membrane trafficking, which abrogates the observed autophagy defects in ΔPaAtg24 by restoring vacuole size and the proper localization of SNARE protein PaSNC1. In addition, an oleic acid diet leads to an altered use of the mitochondrial respiratory chain: complex I and II are bypassed, leading to reduced reactive oxygen species (ROS) production. Overall, our study uncovers multiple effects of an oleic acid diet, which extends the lifespan of P. anserina and provides perspectives to explain the positive nutritional effects on human aging.

The impact of biomembranes and their dynamics on organismic aging: insights from a fungal aging model

“…Metabolization of his carbon source requires peroxisomes ( Figure 4 ). Most interestingly, an oleic acid diet led to a mean lifespan extension of the wild type from 24 to 30 days and from 19 to 37 days of the PaAtg24 -deleted mutant ( Schürmanns et al, 2022 ). This effect occurs along with the formation of lipid droplets, which are used for oleate uptake and its transport to peroxisomes for metabolization.…”

“…In addition, they are active in maintaining membrane homeostasis via the transport of phospholipids to the vacuole membrane. This function became apparent from the analysis of the PaAtg1 -deleted mutant, which was affected in membrane trafficking and in vacuolar function and autophagy ( Henkel et al, 2020 ; Schürmanns et al, 2022 ).…”

“…The induction of lipid droplets by oleic acid occurs not only in the PaAtg24 -deleted mutant but also in the wild type and is correlated with a lifespan extension ( Schürmanns, 2022 ; Schürmanns et al, 2022 ). Apart from the effect of making biomembranes available for vacuole proliferation, an altered bioenergetic metabolism starting with ß-oxidation in peroxisomes is followed by the transfer of peroxisomal FADH 2 and NADH, most likely via specific membrane-bound protein complexes (not shown), to mitochondria ( Wanders et al, 2015 ) and feeding electrons into the RC ( Figure 4 ).…”

“…However, compared to the utilization of fermentable carbon sources, this type of metabolism is strongly reduced when the strains are grown on oleic acid as the sole carbon source. Under these conditions, hydrogen peroxide secretion as a measure of the cellular ROS load is strongly decreased ( Schürmanns et al, 2022 ).…”

Untersuchungen zur Bedeutung selektiver Autophagie für Alterungsprozesse von Podospora anserina

“…Es kann somit davon ausgegangen werden kann, dass die Peroxisomen funktional sind und die Zelle von der Akkumulation dieser Organellen pro昀椀tiert(Henkel et al 2020;Schürmanns 2017). Hierbei scheint ein Ein昀氀uss von Oleat auf die Vakuolengröße vorzuliegen(Schürmanns et al 2022)…”