Independent and sensory human mitochondrial functions reflecting symbiotic evolution DOI Creative Commons
George B. Stefano, Pascal Büttiker,

Simon Weissenberger

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: June 14, 2023

The bacterial origin of mitochondria has been a widely accepted as an event that occurred about 1.45 billion years ago and endowed cells with internal energy producing organelle. Thus, have traditionally viewed subcellular organelle any other – fully functionally dependent on the cell it is part of. However, recent studies given us evidence are more independent than organelles, they can function outside cells, engage in complex “social” interactions, communicate each well cellular components, bacteria viruses. Furthermore, move, assemble organize upon sensing different environmental cues, using process akin to quorum sensing. Therefore, taking all these lines into account we hypothesize need be studied from perspective entity. This view may lead new insights their biological function, inform strategies for treatment disease associated mitochondrial dysfunction.

Language: Английский

Restructured Mitochondrial-Nuclear Interaction in Plasmodium falciparum Dormancy and Persister Survival after Artemisinin Exposure DOI Creative Commons
Sean V. Connelly,

Javier Manzella‐Lapeira,

Zoë C. Levine

et al.

mBio, Journal Year: 2021, Volume and Issue: 12(3)

Published: May 24, 2021

Artemisinin and its semisynthetic derivatives (ART) are fast acting, potent antimalarials; however, their use in malaria treatment is frequently confounded by recrudescences from bloodstream Plasmodium parasites that enter into later reactivate a dormant persister state. Here, we provide evidence the mitochondria of dihydroartemisinin (DHA)-exposed persisters dramatically altered enlarged relative to young, actively replicating ring forms. Restructured mitochondrial-nuclear associations an metabolic state consistent with stress reactive oxygen species. New contacts between nuclei may support communication pathways mitochondrial retrograde signaling, resulting transcriptional changes nucleus as survival response. Further characterization organelle dependencies suggest strategies combat after treatment. IMPORTANCE The major first-line for malaria, especially deadliest form caused falciparum, combination therapy artemisinin-based drug plus partner assure complete cure. Without effective drug, ART administration alone can fail because ability small populations blood-stage survive repeated treatments week or more. Understanding nature dormancy (persisters) wake reestablish propagating parasitemias (recrudesce) exposure improve outcomes counter threats posed develop resistance drugs. show have interactions associated features quiescence. signaling enable responses dormancy.

Language: Английский

Citations

34
A three-organelle complex made by wrappER contacts with peroxisomes and mitochondria responds to liver lipid flux changes DOI Open Access

Nicolò Ilacqua,

Irene Anastasia,

Andrea Raimondi

et al.

Journal of Cell Science, Journal Year: 2021, Volume and Issue: 135(5)

Published: Oct. 21, 2021

Hepatic lipid homeostasis depends on intracellular pathways that respire fatty acid in peroxisomes and mitochondria, systemic secrete into the bloodstream, either free or condensed very-low-density lipoprotein (VLDL) triglycerides. These are interdependent, but it is unclear whether how they integrate a single cellular circuit. Here, we report mouse liver wrappER, distinct endoplasmic reticulum (ER) compartment with apparent acid- VLDL-secretion functions, connects mitochondria. Correlative light electron microscopy, quantitative serial section tomography three-dimensional organelle reconstruction analysis show number of peroxisome-wrappER-mitochondria complexes changes throughout fasting-to-feeding transitions doubles when VLDL synthesis stops following acute genetic ablation Mttp liver. Quantitative proteomic complex-enriched fractions indicates loss upregulates global β-oxidation, thereby integrating dynamics this three-organelle association hepatic flux responses. Therefore, occurs through convergence acid-elimination complex.

Language: Английский

Citations

34
Perspectives on mitochondrial relevance in cardiac ischemia/reperfusion injury DOI Creative Commons
Gaia Pedriali, Daniela Ramaccini, Esmaa Bouhamida

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Dec. 6, 2022

Cardiovascular disease is the most common cause of death worldwide and in particular, ischemic heart holds considerable position. Even if it has been deeply studied, myocardial ischemia-reperfusion injury (IRI) still a side-effect clinical treatment for several diseases: ischemia process itself leads to temporary damage tissue obviously recovery blood flow promptly required even worsens injury. There no doubt that mitochondria play key role pathogenesis IRI: dysfunctions these important organelles alter cell homeostasis survival. It demonstrated during IRI system mitochondrial quality control undergoes alterations with disruption complex balance between processes fusion, fission, biogenesis mitophagy. The fundamental carried out thanks finely regulated connection other such as plasma membrane, endoplasmic reticulum nucleus, therefore impairments inter-organelle communications exacerbate IRI. This review pointed enhance importance network aim focus on potential mitochondria-targeting therapies new approach after reperfusion process.

Language: Английский

Citations

27
LUBAC assembles a ubiquitin signaling platform at mitochondria for signal amplification and transport of NF‐κB to the nucleus DOI Creative Commons
Zhixiao Wu, Lena A. Berlemann, Verian Bader

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(24)

Published: Nov. 18, 2022

Abstract Mitochondria are increasingly recognized as cellular hubs to orchestrate signaling pathways that regulate metabolism, redox homeostasis, and cell fate decisions. Recent research revealed a role of mitochondria also in innate immune signaling; however, the mechanisms how affect signal transduction poorly understood. Here, we show NF‐κB pathway activated by TNF employs platform for amplification shuttling nucleus. treatment induces recruitment HOIP, catalytic component linear ubiquitin chain assembly complex (LUBAC), its substrate NEMO outer mitochondrial membrane, where M1‐ K63‐linked chains generated. is locally transported nucleus mitochondria, leading an increase mitochondria‐nucleus contact sites HOIP‐dependent manner. Notably, TNF‐induced stabilization kinase PINK1 furthermore contributes antagonizing M1‐ubiquitin‐specific deubiquitinase OTULIN. Overall, our study reveals amplifying TNF‐mediated activation, both serving platform, well transport mode nuclear.

Language: Английский

Citations

25
Independent and sensory human mitochondrial functions reflecting symbiotic evolution DOI Creative Commons
George B. Stefano, Pascal Büttiker,

Simon Weissenberger

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: June 14, 2023

The bacterial origin of mitochondria has been a widely accepted as an event that occurred about 1.45 billion years ago and endowed cells with internal energy producing organelle. Thus, have traditionally viewed subcellular organelle any other – fully functionally dependent on the cell it is part of. However, recent studies given us evidence are more independent than organelles, they can function outside cells, engage in complex “social” interactions, communicate each well cellular components, bacteria viruses. Furthermore, move, assemble organize upon sensing different environmental cues, using process akin to quorum sensing. Therefore, taking all these lines into account we hypothesize need be studied from perspective entity. This view may lead new insights their biological function, inform strategies for treatment disease associated mitochondrial dysfunction.

Language: Английский

Citations

16