Disruption of the MICOS complex leads to an aberrant cristae structure and an unexpected, pronounced lifespan extension in Podospora anserina

  • Mitochondria are dynamic eukaryotic organelles involved in a variety of essential cellular processes including the generation of adenosine triphosphate (ATP) and reactive oxygen species as well as in the control of apoptosis and autophagy. Impairments of mitochondrial functions lead to aging and disease. Previous work with the ascomycete Podospora anserina demonstrated that mitochondrial morphotype as well as mitochondrial ultrastructure change during aging. The latter goes along with an age-dependent reorganization of the inner mitochondrial membrane leading to a change from lamellar cristae to vesicular structures. Particularly from studies with yeast, it is known that besides the F1Fo-ATP-synthase and the phospholipid cardiolipin also the “mitochondrial contact site and cristae organizing system” (MICOS) complex, existing of the Mic60- and Mic10-subcomplex, is essential for proper cristae formation. In the present study, we aimed to understand the mechanistic basis of age-related changes in the mitochondrial ultrastructure. We observed that MICOS subunits are coregulated at the posttranscriptional level. This regulation partially depends on the mitochondrial iAAA-protease PaIAP. Most surprisingly, we made the counterintuitive observation that, despite the loss of lamellar cristae and of mitochondrial impairments, the ablation of MICOS subunits (except for PaMIC12) leads to a pronounced lifespan extension. Moreover, simultaneous ablation of subunits of both MICOS subcomplexes synergistically increases lifespan, providing formal genetic evidence that both subcomplexes affect lifespan by different and at least partially independent pathways. At the molecular level, we found that ablation of Mic10-subcomplex components leads to a mitohormesis-induced lifespan extension, while lifespan extension of Mic60-subcomplex mutants seems to be controlled by pathways involved in the control of phospholipid homeostasis. Overall, our data demonstrate that both MICOS subcomplexes have different functions and play distinct roles in the aging process of P. anserina.
Author:Verena WarnsmannORCiDGND, Lisa-Marie Marschall, Anja C. Meeßen, Maike WoltersORCiDGND, Lea SchürmannsORCiDGND, Marion Basoglu, Stefan EimerGND, Heinz D. OsiewaczORCiDGND
Parent Title (English):Journal of cellular biochemistry
Place of publication:New York, NY
Document Type:Article
Date of Publication (online):2022/05/26
Date of first Publication:2022/05/26
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/10/23
Tag:MICOS; Podospora anserina; aging; cristae; mitochondria; mitohormesis
Page Number:21
First Page:1306
Last Page:1326
This study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 25913077–SFB1177 to HDO and SE and Os75/17-2 to HDO. Open Access funding enabled and organized by Projekt DEAL.
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International