The role of mitochondria in rheumatic diseases

Becker, Yann; Duvvuri, Bhargavi; Fortin, Paul R.; Lood, Christian; Boilard, Éric

doi:10.1038/s41584-022-00834-z

Cited by 35 publications

(29 citation statements)

References 281 publications

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“…As a last remark, it should be noted that even though anti-cardiolipin antibodies are usually not tested when ordering AMA laboratory testing, they actually are, per definition, a subtype of AMA. 136 Cardiolipin is one of the main components of the inner mitochondrial membrane, constituting around one-fifth of its lipid composition. 137 Testing for anticardiolipin antibodies is not usually performed in the context of IIM, with only a few case reports describing the co-occurrence of anti-cardiolipin antibodies with other MSA/myositis-associated antibodies.…”

Section: Autoantibodiesmentioning

confidence: 99%

The Emerging Role of Mitochondrial Dysfunction in the Pathogenesis of Idiopathic Inflammatory Myopathies

Gonzalez-Chapa¹,

Macêdo²,

Lood³

2023

Rambam Maimonides Med J

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Increasing evidence points towards mitochondria as crucial players in the initiation and progression of auto-immune and degenerative disorders, to which impaired cell metabolism is but a facet of the subjacent etiopathogenesis. This review aims to introduce the reader to essential concepts of mitochondrial abnormalities in idiopathic inflammatory myopathy (IIM), underscoring inclusion-body myositis and dermatomyositis. Far surpassing the initial simplistic view of being responsible for energy generation, mitochondria have gathered attention regarding their role in inflammatory processes, being able to fuel autoimmunity, as shown by the presence of anti-mitochondrial antibodies (AMAs) in up to 10% of IIM patients. As cellular respiration takes place, mitochondrial metabolites might help to shape the pro-inflammatory milieu in affected muscle, beyond generating reactive oxygen species, which are well-recognized inducers of damage-associated molecular patterns. A series of mitochondrial components might facilitate the sterile activation of pro-inflammatory cells and the production of several cytokines responsible for enhancing auto-immune responses. Marked variation in the mitochondrial genome has also been reported in IIM patients. As such, we summarize key historical and recent advances linking aberrations and instabilities of mitochondrial DNA to impaired muscle function. Besides discussing mitochondrial dysfunction as an essential part of IIM development, we also highlight possible associations between presence of AMAs and a particular phenotype of IIM, with its own characteristic clinical and radiological pattern. Finally, we present promising treatment approaches targeting mitochondria, while briefly discussing experimental models for gaining deeper insight into the disease process, and ultimately leading to novel drug development.

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Section: Autoantibodiesmentioning

confidence: 99%

The Emerging Role of Mitochondrial Dysfunction in the Pathogenesis of Idiopathic Inflammatory Myopathies

Gonzalez-Chapa¹,

Macêdo²,

Lood³

2023

Rambam Maimonides Med J

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“…Mitochondria, also called the “energy factories of cells”, are crucial in energy production and biochemical reactions, including calcium signaling, aerobic metabolism of fat and glucose, oxidative phosphorylation, and apoptosis. − Mitochondrial malfunction is associated with several inherited and acquired diseases . The mitochondria of malignant cells differ physically and functionally from those of healthy cells, and they actively take part in metabolic reprogramming …”

Section: Mitochondria (Types 1–3)mentioning

confidence: 99%

Material-Assisted Engineering of Organelles for Biomedical Applications

Liu

2022

ACS Materials Lett.

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Organelles play significant roles in mediating communication between and within cells. Furthermore, organelle failure would affect cellular homeostasis and result in a variety of pathophysiologies, such as cancer, metabolic, cardiovascular, and neurodegenerative illness. Since healthy and functional organelles with natural biological functions play important roles in the regulation and recovery of defective cells, exosomes, an extracellular organelle, have been used as viable natural vehicles for drug loading and delivery by using physical and chemical engineering techniques. With the development of synthetic chemistry, materials, and nanotechnology, material-assisted engineering of intracellular organelles has received much research interest. In this Review, we summarize four different strategies for isolated intracellular organelle engineering, including electrostatic interaction, hydrophobic interaction, covalent conjugation, and lipid fusion to highlight how man-made and natural materials could be used to modify organelles and make them more powerful for various applications. We expect this Review could encourage further development in organelle painting techniques, and their compatibility with cell biology would result in novel living materials for efficient theragnostic applications.

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“…[8][9][10][11] Extracellular mitochondria were previously described in blood as whole organelles part of EV cargo or as naked organelles (i.e., devoid of any surrounding nonmitochondrial membrane moiety), and their levels can increase in different diseases or conditions. [12][13][14][15] Mitochondria may be emitted by various cell lines, including platelets, and other cell lineages, including astrocytes, eosinophils, mast cells, neurons, neutrophils, endothelial cells, and hematopoietic stem and progenitor cells. 10,13,14,[16][17][18][19][20][21][22] In addition, mitochondria can be transferred to other cells through nanotubes, while vesicles called mitovesicles can bud directly from mitochondria in the cytoplasm and may reach the extracellular milieu through secretion mechanisms yet to be defined, suggesting that mechanisms promoting mitochondrial exchanges between cells may exist.…”

Section: Introductionmentioning

confidence: 99%

Platelet extracellular vesicles and their mitochondrial content improve the mitochondrial bioenergetics of cellular immune recipients

Pelletier,

Breton,

Allaeys

et al. 2023

Transfusion

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BackgroundMitochondria play a critical role in the production of cell energy and the regulation of cell death. Therefore, mitochondria orchestrate numerous cell effector functions, including fine‐tuning the immune system. While mitochondria are mainly found intracellularly, they can escape the confine of the cell during the process of extracellular vesicle release. Platelets patrol blood vessels to ensure vasculature integrity and to support the immune system. In blood, platelets are the primary source of circulating mitochondria. Activated platelets produce extracellular vesicles, including a subset of mitochondria‐containing vesicles.Study Design and MethodsWe characterized mitochondrial functions in platelet‐derived extracellular vesicles, and examined whether they could impact the bioenergetics of cellular immune recipients using an extracellular flux analyzer to measure real‐time bioenergetics.ResultsWe validated that extracellular vesicles derived from activated platelets contain the necessary mitochondrial machinery to respirate and generate energy. Moreover, neutrophils and monocytes efficiently captured platelet‐derived extracellular vesicles, enhancing their mitochondrial fitness. This process required functional mitochondria from donor platelets, as it was abolished by the inactivation of extracellular mitochondria using mitochondrial poison.DiscussionTogether, the data suggest that extracellular mitochondria produced by platelets may support other metabolic functions through transcellular bioenergetics.

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The role of mitochondria in rheumatic diseases

Cited by 35 publications

References 281 publications

The Emerging Role of Mitochondrial Dysfunction in the Pathogenesis of Idiopathic Inflammatory Myopathies

The Emerging Role of Mitochondrial Dysfunction in the Pathogenesis of Idiopathic Inflammatory Myopathies

Material-Assisted Engineering of Organelles for Biomedical Applications

Platelet extracellular vesicles and their mitochondrial content improve the mitochondrial bioenergetics of cellular immune recipients

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