bims-miptne 2024-09-15 papers

EMBO J. 2024 Sep 11.

Systematic mapping of mitochondrial calcium uniporter channel (MCUC)-mediated calcium signaling networks.

The mitochondrial calcium uniporter channel (MCUC) mediates mitochondrial calcium entry, regulating energy metabolism and cell death. Although several MCUC components have been identified, the molecular basis of mitochondrial calcium signaling networks and their remodeling upon changes in uniporter activity have not been assessed. Here, we map the MCUC interactome under resting conditions and upon chronic loss or gain of mitochondrial calcium uptake. We identify 89 high-confidence interactors that link MCUC to several mitochondrial complexes and pathways, half of which are associated with human disease. As a proof-of-concept, we validate the mitochondrial intermembrane space protein EFHD1 as a binding partner of the MCUC subunits MCU, EMRE, and MCUB. We further show a MICU1-dependent inhibitory effect of EFHD1 on calcium uptake. Next, we systematically survey compensatory mechanisms and functional consequences of mitochondrial calcium dyshomeostasis by analyzing the MCU interactome upon EMRE, MCUB, MICU1, or MICU2 knockdown. While silencing EMRE reduces MCU interconnectivity, MCUB loss-of-function leads to a wider interaction network. Our study provides a comprehensive and high-confidence resource to gain insights into players and mechanisms regulating mitochondrial calcium signaling and their relevance in human diseases.

Keywords: Calcium Signaling; Mitochondria; Mitochondrial Calcium Uniporter; Organelle; Proteomics

DOI: https://doi.org/10.1038/s44318-024-00219-w

Discov Nano. 2024 Sep 07. 19(1): 143

Enhanced drug delivery with nanocarriers: a comprehensive review of recent advances in breast cancer detection and treatment.

Ruby Dhiman, Nancy Bazad, Riya Mukherjee, Himanshu, Gunjan, Elcio Leal, Saheem Ahmad, Kirtanjot Kaur, V Samuel Raj, Chung-Ming Chang, Ramendra Pati Pandey.

Breast cancer (BC) remains a leading cause of morbidity and mortality among women worldwide, with triple-negative breast cancer (TNBC) posing significant treatment challenges due to its aggressive phenotype and resistance to conventional therapies. Recent advancements in nanocarrier technology offer promising solutions for enhancing drug delivery, improving bioavailability, and increasing drug accumulation at tumor sites through targeted approaches. This review delves into the latest innovations in BC detection and treatment, highlighting the role of nanocarriers like polymeric micelles, liposomes, and magnetic nanoparticles in overcoming the limitations of traditional therapies. Additionally, the manuscript discusses the integration of cutting-edge diagnostic tools, such as multiplex PCR-Nested Next-Generation Sequencing (mPCR-NGS) and blood-based biomarkers, which are revolutionizing early detection and molecular profiling of BC. The convergence of these technologies not only enhances therapeutic outcomes but also paves the way for personalized medicine in BC management. This comprehensive review underscores the potential of nanocarriers in transforming BC treatment and emphasizes the critical importance of early detection in improving patient prognosis.

Keywords: Breast cancer; Diagnostic; Nanocarriers; Tumor location

DOI: https://doi.org/10.1186/s11671-024-04086-6

Cell Signal. 2024 Sep 07. pii: S0898-6568(24)00364-4. [Epub ahead of print] 111396

Small molecules targeting mitochondria as an innovative approach to cancer therapy.

Omkar S Kamble, Rana Chatterjee, K G Abishek, Jyoti Chandra, Abdulrhman Alsayari, Shadma Wahab, Amirhossein Sahebkar, Prashant Kesharwani, Rambabu Dandela.

Cellular death evasion is a defining characteristic of human malignancies and a significant contributor to therapeutic inefficacy. As a result of oncogenic inhibition of cell death mechanisms, established therapeutic regimens seems to be ineffective. Mitochondria serve as the cellular powerhouses, but they also function as repositories of self-destructive weaponry. Changes in the structure and activities of mitochondria have been consistently documented in cancer cells. In recent years, there has been an increasing focus on using mitochondria as a targeted approach for treating cancer. Considerable attention has been devoted to the development of delivery systems that selectively aim to deliver small molecules called "mitocans" to mitochondria, with the ultimate goal of modulating the physiology of cancer cells. This review summarizes the rationale and mechanism of mitochondrial targeting with small molecules in the treatment of cancer, and their impact on the mitochondria. This paper provides a concise overview of the reasoning and mechanism behind directing treatment towards mitochondria in cancer therapy, with a particular focus on targeting using small molecules. This review also examines diverse small molecule types within each category as potential therapeutic agents for cancer.

Keywords: Apoptosis; Mitocans; Mitochondrial targeting; Small molecules; cancer

DOI: https://doi.org/10.1016/j.cellsig.2024.111396