Mitochondrial signal transduction

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1620 - 1653

Published: Nov. 1, 2022

The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue the processor cell, together with nucleus other they constitute mitochondrial information processing system (MIPS). In a three-step process, (1) sense respond to both endogenous environmental inputs through morphological functional remodeling; (2) integrate network-based physical interactions diffusion mechanisms; (3) produce output signals tune functions systemically regulate physiology. This input-to-output transformation allows metabolic, biochemical, neuroendocrine, local or systemic enhance organismal adaptation. An explicit focus on signal transduction emphasizes role communication in biology. framework also opens new avenues understand how mediate inter-organ processes underlying human health.

Language: Английский

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Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment

Science, Journal Year: 2022, Volume and Issue: 378(6617)

Published: Oct. 20, 2022

Full-grown oocytes are transcriptionally silent and must stably maintain the messenger RNAs (mRNAs) needed for oocyte meiotic maturation early embryonic development. However, where how mammalian store maternal mRNAs is unclear. Here, we report that accumulate in a mitochondria-associated ribonucleoprotein domain (MARDO). MARDO assembly around mitochondria was promoted by RNA-binding protein ZAR1 directed an increase mitochondrial membrane potential during growth. foci coalesced into hydrogel-like matrices clustered mitochondria. Maternal stored were translationally repressed. Loss of disrupted MARDO, dispersed mitochondria, caused premature loss MARDO-localized mRNAs. Thus, membraneless compartment controls distribution regulates mRNA storage, translation, decay to ensure fertility mammals.

Language: Английский

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Making a good egg: human oocyte health, aging, and in vitro development

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2623 - 2677

Published: May 12, 2023

Mammalian eggs (oocytes) are formed during fetal life and establish associations with somatic cells to form primordial follicles that create a store of germ (the pool). The size this pool is influenced by key events the formation factors influence subsequent activation follicle growth. These regulatory pathways must ensure reserve oocytes within in humans lasts for up 50 years, yet only approximately 0.1% will ever be ovulated rest undergoing degeneration. This review outlines mechanisms govern processes oocyte later growth, ovarian stroma, through ovulation particular reference human oocytes/follicles. In addition, effects aging on female reproductive capacity changes number quality emphasized, both cellular clinical implications discussed. Finally, details current developments culture systems support all stages growth generate mature vitro emerging prospects making new from stem outlined.

Language: Английский

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RNA granules: functional compartments or incidental condensates?

Genes & Development, Journal Year: 2023, Volume and Issue: 37(9-10), P. 354 - 376

Published: May 1, 2023

RNA granules are mesoscale assemblies that form in the absence of limiting membranes. contain factors for biogenesis and turnover often assumed to represent specialized compartments biochemistry. Recent evidence suggests assemble by phase separation subsoluble ribonucleoprotein (RNP) complexes partially demix from cytoplasm or nucleoplasm. We explore possibility some nonessential condensation by-products arise when RNP exceed their solubility limit as a consequence cellular activity, stress, aging. describe use evolutionary mutational analyses single-molecule techniques distinguish functional "incidental condensates."

Language: Английский

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Mouse oocytes sequester aggregated proteins in degradative super-organelles

Cell, Journal Year: 2024, Volume and Issue: 187(5), P. 1109 - 1126.e21

Published: Feb. 1, 2024

Oocytes are among the longest-lived cells in body and need to preserve their cytoplasm support proper embryonic development. Protein aggregation is a major threat for intracellular homeostasis long-lived cells. How oocytes cope with protein during extended life unknown. Here, we find that mouse accumulate aggregates specialized compartments named endolysosomal vesicular assemblies (ELVAs). Combining live-cell imaging, electron microscopy, proteomics, found ELVAs non-membrane-bound composed of endolysosomes, autophagosomes, proteasomes held together by matrix formed RUFY1. Functional assays revealed immature oocytes, sequester aggregated proteins, including TDP-43, degrade them upon oocyte maturation. Inhibiting degradative activity leads accumulation embryo detrimental survival. Thus, represent strategy safeguard

Language: Английский

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Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1504 - 1504

Published: Jan. 25, 2024

Type 2 diabetes (T2D) is a heterogenous disease, and conventionally, peripheral insulin resistance (IR) was thought to precede islet β-cell dysfunction, promoting progression from prediabetes T2D. New evidence suggests that T2D-lean individuals experience early dysfunction without significant IR. Regardless of the primary event (i.e., IR vs. dysfunction) contributes dysglycemia, early-onset oxidative damage mitochondrial in multiple metabolic tissues may be driver T2D onset progression. Oxidative stress, defined as generation reactive oxygen species (ROS), mediated by hyperglycemia alone or combination with lipids. Physiological stress promotes inter-tissue communication, while pathological mis-communication, new this via extracellular vesicles (EVs), including mitochondria containing EVs. Under metabolic-related conditions, EV-mediated cross-talk between β-cells skeletal muscle likely trigger anomalies leading This article reviews underlying molecular mechanisms ROS-related pathogenesis prediabetes, mitophagy dynamics due stress. Further, review will describe potential various therapeutic avenues for attenuating damage, reversing preventing

Language: Английский

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Rejuvenation of aged oocyte through exposure to young follicular microenvironment

Nature Aging, Journal Year: 2024, Volume and Issue: 4(9), P. 1194 - 1210

Published: Sept. 9, 2024

Language: Английский

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Mitochondrial heterogeneity and adaptations to cellular needs

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(5), P. 674 - 686

Published: May 1, 2024

Language: Английский

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Current methods in explainable artificial intelligence and future prospects for integrative physiology

Pflügers Archiv - European Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Explainable artificial intelligence (XAI) is gaining importance in physiological research, where now used as an analytical and predictive tool for many medical research questions. The primary goal of XAI to make AI models understandable human decision-makers. This can be achieved particular through providing inherently interpretable methods or by making opaque their outputs transparent using post hoc explanations. review introduces core topics provides a selective overview current physiology. It further illustrates solved discusses open challenges existing practical examples from the field. article gives outlook on two possible future prospects: (1) provide trustworthy integrative (2) integrating expertise about explanation into method development useful beneficial human-AI partnerships.

Language: Английский

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A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Aug. 2, 2022

In humans and other mammals, germline mutations are more likely to arise in fathers than mothers. Although this sex bias has long been attributed DNA replication errors spermatogenesis, recent evidence from points the importance of mutagenic processes that do not depend on cell division, calling into question our understanding basic phenomenon. Here, we infer ratio paternal-to-maternal mutations,

Language: Английский

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