bims-migras 2025-05-18 papers

Issue of 2025–05–18
four papers selected by
Cliff Dominy

Front Pharmacol. 2025 ;16 1563800

Macrophage-driven exosomes regulate the progression of cardiovascular disease.

Liao Qi, De-Zhu Luo, HuLi Li, JianWen Yan, WenJie He.

Exosomes, as vital mediators of intercellular communication, play a critical role in the progression of cardiovascular disease (CVD). Recently, macrophage-derived exosomes (Mφ-Exos) have garnered increasing attention because of their significant potential in early diagnosis, pathological processes, and therapeutic applications for CVD. Exosomes contain diverse nucleic acids (e.g., miRNAs, mRNAs, and long noncoding RNAs (lncRNAs)) and proteins, which serve as specific biomarkers that regulate various stages of CVD. For example, miRNAs encapsulated within exosomes (e.g., miR-21, miR-133a, and miR-155) are closely associated with atherosclerosis, myocardial infarction, coronary artery disease, and stroke, and changes in their abundance can serve as diagnostic and prognostic indicators. Additionally, the composition of Mφ-Exos, including miRNAs, lipids, and proteins, plays a significant role in the initiation, progression, and inflammation of CVD. Research on Mφ-Exos provides new directions for early diagnosis, mechanistic exploration, and novel therapeutic targets in CVD. However, challenges remain regarding exosome isolation and identification technologies. Future studies need to further explore the biological properties of exosomes and develop more efficient, economical, and straightforward isolation methods. This review summarizes the multifaceted regulatory roles of Mφ-Exos in CVD, encompassing key processes such as inflammation, angiogenesis, metabolism, and cell death. Research has shown that M1-Exos promote the progression and exacerbation of CVD through pro-inflammatory and pro-fibrotic mechanisms, while M2-Exos demonstrate significant therapeutic potential via anti-inflammatory, pro-angiogenic, and metabolic reprogramming pathways. These findings not only reveal the complex mechanisms of Mφ-Exos in CVD but also provide new perspectives and potential targets for early diagnosis and precision treatment of the disease.

Keywords: cardiovascular disease; exosomes; extracellular vesicles; inflamation; macrophage polarization

DOI: https://doi.org/10.3389/fphar.2025.1563800

J Cell Sci. 2025 May 01. pii: jcs263895. [Epub ahead of print]138(9):

Mitochondria-membranous organelle contacts at a glance.

Antigoni Diokmetzidou, Luca Scorrano.

Mitochondrial contact sites are specialized interfaces where mitochondria physically interact with other organelles. Stabilized by molecular tethers and defined by unique proteomic and lipidomic profiles, these sites enable direct interorganellar communication and functional coordination, playing crucial roles in cellular physiology and homeostasis. Recent advances have expanded our knowledge of contact site-resident proteins, illuminated the dynamic and adaptive nature of these interfaces, and clarified their contribution to pathophysiology. In this Cell Science at a Glance article and the accompanying poster, we summarize the mitochondrial contacts that have been characterized in mammals, the molecular mechanisms underlying their formation, and their principal functions.

Keywords: Contact sites; Mitochondria; Organelles

DOI: https://doi.org/10.1242/jcs.263895

Cell Death Discov. 2025 May 10. 11(1): 231

Physiological roles and therapeutic implications of USP6.

Suaad Syed, Muhammad Yasir Khan Painda, Dawood Ghafoor, Dongjin Gu, Feng Wang.

Ubiquitin-specific protease 6 (USP6) is a member of deubiquitinating enzyme family, recognized for its essential roles in physiological and pathological processes. USP6 is initially identified as a hominoid-specific enzyme residing on chromosome 17p13. USP6 is involved in regulating cellular functions, signaling pathways, protein degradation, intracellular trafficking, tumorigenesis and immune responses. USP6 is pivotal in signaling pathways, including NF-κB, JAK-STAT, and Wnt, which are fundamental for maintaining cellular homeostasis and mediating stress responses. Dysregulation of USP6 has been implicated in a spectrum of diseases, including bone tumors, breast and colorectal cancers, cranial fasciitis, and neurological disorders such as memory dysfunction. Furthermore, USP6 is involved in emerging therapeutic strategies highlighting its implications for drug development. A number of potential small molecule inhibitors are known to be responsible for suppression of USP6, such as Momelotinib (CYT387), FT385, USP30 Inh-1, -2 and -3, 2,6-Diaminopyridine-3,5-bis(thiocyanate) (PR-619) and so on. This review explores the emerging role of USP6 as a key regulator of cellular signaling pathways, its involvement in disease progression, its physiological functions, and the inhibitors that effectively suppress USP6 activity in detail. The comprehensive study provides insight to enhance our understanding of biological importance and therapeutic interventions of USP6 in drug development.

DOI: https://doi.org/10.1038/s41420-025-02466-0

J Cereb Blood Flow Metab. 2025 May 14. 271678X251338971

Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components.

Mingjin Wang, Weida Wang, Michael Chopp, Zheng Gang Zhang, Yi Zhang.

Extracellular vesicles (EVs) facilitate the transfer of biological materials between cells throughout the body. Mitochondria, membrane-bound organelles present in the cytoplasm of nearly all eukaryotic cells, are vital for energy production and cellular homeostasis. Recent studies highlight the critical role of the transport of diverse mitochondrial content, such as mitochondrial DNA (mt-DNA), mitochondrial RNA (mt-RNA), mitochondrial proteins (mt-Prots), and intact mitochondria by small EVs (<200 nm) and large EVs (>200 nm) to recipient cells, where these cargos contribute to cellular and mitochondrial homeostasis. The interplay between EVs and mitochondrial components has significant implications for health, metabolic regulation, and potential as biomarkers. Despite advancements, the mechanisms governing EV-mitochondria crosstalk and the regulatory effect of mitochondrial EVs remain poorly understood. This review explores the roles of EVs and their mitochondrial cargos in health and disease, examines potential mechanisms underlying their interactions, and emphasizes the therapeutic potential of EVs for neurological and systemic conditions associated with mitochondrial dysfunction.

Keywords: Extracellular vesicles; energy metabolism; mitochondria; mitochondrial components

DOI: https://doi.org/10.1177/0271678X251338971