Biology subjects

Kroczek, L.

Publications and source records attributed to Kroczek, L..

3 recordsLinked to original sources

bioRxiv2025

Stress adaptation of mitochondrial protein import by OMA1-mediated degradation of DNAJC15

Mitochondria adapt to cellular stress to ensure cell survival. The stress-regulated mitochondrial peptidase OMA1 orchestrates these adaptive responses, which limit mitochondrial fusion and promote mitochondrial stress signaling and metabolic rewiring. Here, we show that cellular stress adaptation involves OMA1-mediated regulation of mitochondrial protein import and OXPHOS biogenesis. OMA1 cleaves the mitochondrial chaperone DNAJC15 and promotes its degradation by the m-AAA protease AFG3L2. Loss of DNAJC15 reduces the import of OXPHOS-related proteins via the TIMM23-TIMM17A protein translocase, limiting OXPHOS biogenesis under conditions of mitochondrial dysfunction. Non-imported mitochondrial preproteins accumulate at the endoplasmic reticulum and induce an ATF6-related unfolded protein response. Our results demonstrate stress-dependent changes in protein import specificity as part of the OMA1-mediated mitochondrial stress response and highlight the interdependence of proteostasis regulation between different organelles.

cell biology↗

bioRxiv2023

Specialized pathogenic cells release Tc toxins using a type 10 secretion system

Disease-causing bacteria use a variety of secreted toxins to invade and subjugate their hosts. While the machinery responsible for secretion of many smaller toxins has already been established, it remains enigmatic for larger ones such as Tc toxins from human and insect pathogens, which approach the size of a prokaryotic ribosome. In the present study, we combine targeted genomic editing, proteomic profiling and cryo-electron tomography of the insect pathogen Yersinia entomophaga to reveal that a specialized subset of bacterial cells produces the Tc toxin YenTc as part of a complex toxin cocktail released into the environment by controlled cell lysis using a transcriptionally-coupled, pH-dependent type 10 secretion system (T10SS). Our results dissect the process of Tc toxin export by a T10SS in hitherto unprecedented detail, identifying that T10SSs operate via a previously unknown lytic mode of action, and establishing them as crucial players in the size-insensitive release of cytoplasmically folded toxins. With T10SSs directly embedded in Tc toxin operons of major human pathogens such as Yersinia pestis and Salmonella enterica, we anticipate our findings to model an important aspect of pathogenesis in bacteria with a significant impact on global human health.

microbiology↗

bioRxiv2022

Metabolic rewiring of mitochondria in senescence revealed by time-resolved analysis of the mitochondrial proteome

Mitochondrial dysfunction and cellular senescence are hallmarks of aging. However, the relationship between these two phenomena remains incompletely understood. In this study, we investigated the rewiring of mitochondria upon development of the senescent state in human IMR90 fibroblasts. Determining the bioenergetic activities and abundance of mitochondria, we demonstrate that senescent cells accumulate mitochondria with reduced OXPHOS activity, resulting in an overall increase of mitochondrial activities in senescent cells. Time-resolved proteomic analyses revealed extensive reprogramming of the mitochondrial proteome upon senescence development and allowed the identification of metabolic pathways that are rewired with different kinetics upon establishment of the senescent state. Among the early-responding pathways, the degradation of branched-chain amino acid (BCAA) was increased, while the one carbon-folate metabolism was decreased. Late-responding pathways include lipid metabolism and mitochondrial translation. These signatures were confirmed by metabolic tracing experiments, highlighting metabolic rewiring as a central feature of mitochondria in cellular senescence. Together, our data provide an unprecedentedly comprehensive view on the metabolic status of mitochondria in senescent cells and reveal how the mitochondrial proteome adapts to the induction of senescence.

cell biology↗