Lysosomes are an integral part of the intracellular defense system against microbes. Lysosomal homeostasis in the host is adaptable and responds to conditions such as infection or nutritional deprivation. Pathogens such as () and avoid lysosomal targeting by actively manipulating the host vesicular trafficking and reside in a vacuole altered from the default lysosomal trafficking. In this review, the mechanisms by which the respective pathogen containing vacuoles (PCVs) intersect with lysosomal trafficking pathways and maintain their distinctness are discussed. Despite such active inhibition of lysosomal targeting, emerging literature shows that different pathogens or pathogen derived products exhibit a global influence on the host lysosomal system. Pathogen mediated lysosomal enrichment promotes the trafficking of a sub-set of pathogens to lysosomes, indicating heterogeneity in the host-pathogen encounter. This review integrates recent advancements on the global lysosomal alterations upon infections and the host protective role of the lysosomes against these pathogens. The review also briefly discusses the heterogeneity in the lysosomal targeting of these pathogens and the possible mechanisms and consequences.
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http://dx.doi.org/10.3389/fcimb.2020.595502 | DOI Listing |
Autophagy
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Glia contribute to the neuropathology of Parkinson disease (PD), but how they react opposingly to be beneficial or detrimental under pathological conditions, like promoting or eliminating SNCA/α-syn (synuclein alpha) inclusions, remains elusive. Here we present evidence that aux (auxilin), the homolog of the PD risk factor GAK (cyclin G associated kinase), regulates the lysosomal degradation of SNCA/α-syn in glia. Lack of glial GAK/aux increases the lysosome number and size, regulates lysosomal acidification and hydrolase activity, and ultimately blocks the degradation of substrates including SNCA/α-syn.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Key Laboratory of Pharmacognosy, College of Pharmacy, Guilin Medical University, Guilin, China.
Natural products are valuable medicinal resources in the field of anti-inflammation due to their significant bioactivity and low antibiotic resistance. Research has demonstrated that many natural products exert notable anti-inflammatory effects by modulating the Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) signaling pathways. The research on related signal transduction mechanisms and pharmacological mechanisms is increasingly being discovered and validated.
View Article and Find Full Text PDFFront Mol Neurosci
January 2025
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Mitochondria and lysosomes are critical for neuronal homeostasis, as highlighted by their dysfunction in various neurological diseases. Recent studies have identified dynamic membrane contact sites between mitochondria and lysosomes, independent of mitophagy and the lysosomal degradation of mitochondrial-derived vesicles (MDVs), allowing bidirectional crosstalk between these cell compartments, the dynamic regulation of organelle networks, and substance exchanges. Emerging evidence suggests that abnormalities in mitochondria-lysosome contact sites (MLCSs) contribute to neurological diseases, including Parkinson's disease, Charcot-Marie-Tooth (CMT) disease, lysosomal storage diseases, and epilepsy.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
University of Science and Technology of China, Department of Chemistry, 96 JinZhai Road, 230026, Hefei, CHINA.
Environment-recognizing DNA nanodevices have proven promising for cellular manipulation and disease treatment, whereas how to sequentially respond to different cellular microenvironments remains a challenge. To this end, here we elaborate a logic-gated intelligent DNA nanorobot (Gi-DR) for the cascade response to inter- and intra-cellular microenvironments, thereby achieving lysosome-targeted cargo delivery for subcellular interference and tumor treatment with enhanced efficacy. Utilizing G-quadruplexes to respond to high-level K+ in cancer cell surrounding, this Gi-DR nanorobot can activate an aptamer-based transmembrane DNA machine that delivers molecular payloads to cellular lysosome.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University of Chinese Medicine, Nanjing, 210000, Jiangsu, China.
Gastric cancer (GC) is a prevalent malignant tumor of the digestive system that is often diagnosed at advanced stages owing to inconspicuous early symptoms and a lack of specific examination methods. Effective treatment of advanced stages remains challenging, emphasizing the need for new therapeutic targets. Metabolic reprogramming, a hallmark of tumors, plays a pivotal role in tumor progression, immune evasion, and immune surveillance.
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