Mitochondria on the move: Horizontal mitochondrial transfer in disease and health

The Journal of Cell Biology, Год журнала: 2023, Номер 222(3)

Опубликована: Фев. 16, 2023

Mammalian genes were long thought to be constrained within somatic cells in most cell types. This concept was challenged recently when cellular organelles including mitochondria shown move between mammalian culture via cytoplasmic bridges. Recent research animals indicates transfer of cancer and during lung injury vivo, with considerable functional consequences. Since these pioneering discoveries, many studies have confirmed horizontal mitochondrial (HMT) its characteristics consequences been described. Additional support for this phenomenon has come from phylogenetic studies. Apparently, trafficking occurs more frequently than previously contributes diverse processes bioenergetic crosstalk homeostasis, disease treatment recovery, development resistance therapy. Here we highlight current knowledge HMT cells, focusing primarily on vivo systems, contend that process is not only (patho)physiologically relevant, but also can exploited the design novel therapeutic approaches.

Язык: Английский

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Sirtuins mediate mitochondrial quality control mechanisms: a novel therapeutic target for osteoporosis

Frontiers in Endocrinology, Год журнала: 2024, Номер 14

Опубликована: Янв. 8, 2024

Mitochondria plays a role in cell differentiation and apoptosis processes. Maintaining mitochondrial function is critical, this involves various aspects of quality control such as protein homeostasis, biogenesis, dynamics, mitophagy. Osteoporosis, metabolic bone disorder, primarily arises from two factors: the dysregulation between lipogenic osteogenic aging marrow mesenchymal stem cells, imbalance osteoblast-mediated formation osteoclast-mediated resorption. Mitochondrial has potential to mitigate or even reverse effects. Among Sirtuin family, consisting seven Sirtuins (SIRT1-7), SIRT1-SIRT6 play crucial maintaining control. Additionally, SIRT1, SIRT3, SIRT6, SIRT7 are directly involved normal development homeostasis by modulating cells. However, precise mechanism which these exert their effects remains unclear. This article reviews impact on osteoporosis, focusing how SIRT6 can improve osteoporosis regulating Furthermore, we provide an overview current state clinical preclinical drugs that activate osteoporosis. Specific Sirtuin-activating compounds effective, but further studies needed. The findings study may offer valuable insights for future research prevention therapeutic target strategies.

Язык: Английский

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Mitochondria Define Intestinal Stem Cell Differentiation Downstream of a FOXO/Notch Axis

Cell Metabolism, Год журнала: 2020, Номер 32(5), С. 889 - 900.e7

Опубликована: Ноя. 1, 2020

Differential WNT and Notch signaling regulates differentiation of Lgr5+ crypt-based columnar cells (CBCs) into intestinal cell lineages. Recently we showed that mitochondrial activity supports CBCs, while adjacent Paneth (PCs) show reduced activity. This implies CBC PCs involves a metabolic transition toward downregulation dependency. Here Forkhead box O (FoxO) transcription factors interact in determining fate. In agreement with the organoid data, Foxo1/3/4 deletion mouse intestine induces secretory differentiation. Importantly, FOXO converge on regulation fission, which turn provokes stem goblet PCs. Finally, scRNA-seq-based reconstruction trajectories role FOXO, Notch, mitochondria Together, this points at new signaling-metabolic axis highlights importance

Язык: Английский

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Mitochondrial Transfer and Regulators of Mesenchymal Stromal Cell Function and Therapeutic Efficacy

Frontiers in Cell and Developmental Biology, Год журнала: 2020, Номер 8

Опубликована: Дек. 7, 2020

Mesenchymal stromal cell (MSC) metabolism plays a crucial role in the surrounding microenvironment both normal physiology and pathological conditions. While MSCs predominantly utilize glycolysis their native hypoxic niche within bone marrow, new evidence reveals importance of upregulation mitochondrial activity MSC function differentiation. Mitochondria regulators such as sirtuins play key roles homeostasis differentiation into mature lineages hematopoietic niche, including osteoblasts adipocytes. The metabolic state represents fine balance between intrinsic needs cellular constraints imposed by extrinsic In context injury inflammation, respond to reactive oxygen species (ROS) damage-associated molecular patterns (DAMPs), damaged mitochondria products, donation injured cells. Through intercellular trafficking, modulation ROS, modification nutrient utilization, endogenous therapies are believed exert protective effects regulation tissues. Similarly, these same mechanisms can be hijacked malignancy whereby transfer and/or DNA (mtDNA) cancer cells increases content enhances oxidative phosphorylation (OXPHOS) favor proliferation invasion. tumor initiation, growth, resistance treatment is debated, but ability modify environment suggests that centrally poised alter malignancy. this review, we describe emerging for adaptations bioenergetics orchestrate developmental fate decisions contribute progression. We discuss potential strategies therapeutic targeting regenerative medicine tissue repair. Lastly, highlight recent progress understanding contribution reprogramming malignancies how alterations promote immunosuppression chemoresistance. Better repair progression promises broaden options clinical oncology.

Язык: Английский

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Mitochondrial Dynamics: Fission and Fusion in Fate Determination of Mesenchymal Stem Cells

Frontiers in Cell and Developmental Biology, Год журнала: 2020, Номер 8

Опубликована: Окт. 15, 2020

Mesenchymal stem cells (MSCs) are pivotal to tissue homeostasis, repair, and regeneration due their potential for self-renewal, multilineage differentiation, immune modulation. Mitochondria highly dynamic organelles that maintain morphology via continuous fission fusion, also known as mitochondrial dynamics. MSCs undergo specific dynamics during proliferation, migration, apoptosis, or aging. Emerging evidence suggests key contributors cell fate determination. The coordination of fusion is crucial cellular function stress responses, while abnormal and/or causes MSC dysfunction. This review focuses on the role in commitment under physiological conditions. We highlight mechanistic insights into modulating strategies cell-based regenerative medicine. These findings shed light contribution MSC-based repair

Язык: Английский

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siVAE: interpretable deep generative models for single-cell transcriptomes

Genome biology, Год журнала: 2023, Номер 24(1)

Опубликована: Фев. 20, 2023

Abstract Neural networks such as variational autoencoders (VAE) perform dimensionality reduction for the visualization and analysis of genomic data, but are limited in their interpretability: it is unknown which data features represented by each embedding dimension. We present siVAE, a VAE that interpretable design, thereby enhancing downstream tasks. Through interpretation, siVAE also identifies gene modules hubs without explicit network inference. use to identify whose connectivity associated with diverse phenotypes iPSC neuronal differentiation efficiency dementia, showcasing wide applicability generative models analysis.

Язык: Английский

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Multifaceted roles of mitochondria in wound healing and chronic wound pathogenesis

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Сен. 11, 2023

Mitochondria are intracellular organelles that play a critical role in numerous cellular processes including the regulation of metabolism, stress response, and cell fate. themselves subject to well-orchestrated order maintain organelle homeostasis. Wound healing is multifactorial process involves stringent several types processes. In event dysregulated wound healing, hard-to-heal chronic wounds form can place significant burden on healthcare systems. Importantly, treatment options remain limited owing nature pathogenesis. One area has received more attention recent years mitochondria healing. With regards this, current literature demonstrated an important for areas pathogenesis apoptosis, redox signalling. Additionally, influence mitochondrial dynamics mitophagy also been investigated. However, few studies have utilised patient tissue when studying instead using various animal models. this review we dissect knowledge discuss how future research potentially aid progression research.

Язык: Английский

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Mitochondria-targetable small molecule fluorescent probes for the detection of cancer-associated biomarkers: A review

Analytica Chimica Acta, Год журнала: 2023, Номер 1289, С. 342060 - 342060

Опубликована: Ноя. 25, 2023

Язык: Английский

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Mitochondrial Dysfunction at the Center of Cancer Therapy

Antioxidants and Redox Signaling, Год журнала: 2019, Номер 32(5), С. 309 - 330

Опубликована: Окт. 3, 2019

Significance: Mitochondria undergo constant morphological changes through fusion, fission, and mitophagy. As the key organelle in cells, mitochondria are responsible for numerous essential cellular functions such as metabolism, regulation of calcium (Ca2+), generation reactive oxygen species, initiation apoptosis. Unsurprisingly, mitochondrial dysfunctions underlie many pathologies including cancer. Recent Advances: Currently, gold standard cancer treatment is chemotherapy, radiation, surgery. However, efficacy these treatments varies across different cells. It has been suggested that may be at center diverse responses. In past decade, significant advances have made understanding distinct types Through investigations underlying mechanisms, more effective options developed. Critical Issues: We summarize various progression led to development therapeutic options. Current mitochondrial-targeted therapies challenges discussed. Future Directions: To address “root” cancer, utilization therapy target stem cells valuable. Investigation other areas trafficking offer new insights into therapy. Moreover, common antibiotics could explored mitocans, synthetic lethality screens can utilized overcome plasticity

Язык: Английский

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Mechanisms of the Metabolic Shift during Somatic Cell Reprogramming

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(9), С. 2254 - 2254

Опубликована: Май 7, 2019

Pluripotent stem cells (PSCs), including embryonic (ESCs) and induced pluripotent (iPSCs), hold a huge promise for regenerative medicine, drug development, disease modeling. PSCs have unique metabolic features that are akin to those of cancer cells, in which glycolysis predominates produce energy as well building blocks cellular components. Recent studies indicate the metabolism is not mere consequence their preference low oxygen environment, but an active process maintaining self-renewal pluripotency, possibly preparation rapid response demands differentiation. Understanding regulatory mechanisms this essential proper derivation, generation, maintenance PSCs. In review, we discuss describe current understanding shift during reprogramming from somatic iPSCs, switches oxidative phosphorylation (OxPhos) glycolysis.

Язык: Английский

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