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Why defects in mitochondria are beneficial for longevity?

The surprising discovery of Maria Sladowska et al. was just published in PLOS Biology


Proteins are the workhorses in the cell. However, the excess of their dysfunctional forms is dangerous. Thus, protein degradation mechanisms evolved to clear such proteins. One major protein clearance pathway involves a complex machine called the proteasome.


The group of scientists working together with Prof. Agnieszka Chacinska and Dr. Ulrike Topf discovered that increasing cellular capacity for protein degradation is beneficial for longevity of a model multicellular organism, the worm Caenorhabditis elegans. Surprisingly, this effect is regulated by mitochondria, which are indispensable organelles required for energy conversion and known as “powerhouses” of the cell. Their dysfunction frequently results in severe diseases. However, the study further demonstrates that under conditions of mild mitochondrial stress a beneficial response involving proteasome activation leads to life span extension of the animals. This discovery provides a surprising explanation that links mild mitochondrial dysfunction and proteasomal activity with direct relevance to mechanisms that promote longevity.


The study has been developed in the Laboratory of Mitochondrial Biogenesis led by Agnieszka Chacinska and the Laboratory of Molecular Basis of Aging and Rejuvenation led by Ulrike Topf, previously a postdoc with Agnieszka and since 2018 a group leader in Institute of Biochemistry and Biophysics since 2018. Dr. Michal Turek, a first co-author of the study, has recently established his group in the Institute of Biochemistry and Biophysics. Agnieszka and her group are currently at the CeNT, University of Warsaw and soon move to IMol Polish Academy of Sciences, in which Agnieszka serves as a Director.


Read: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001302


Full reference:

Sladowska M, Turek M, Kim M-J, Drabikowski K, Mussulini BHM, Mohanraj K, Serwa RA, Topf U and Chacinska A (2021) Proteasome activity contributes to prosurvival response upon mild mitochondrial stress in Caenorhabditis elegans. PLoS Biol 19(7):e3001302.

Maria Sladowska and Michal Turek are equally contributing first authors. Correspondence: Ulrike Topf, Agnieszka Chacinska


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