Map1lc3b-KO Mouse

Map1lc3b, also known as microtubule-associated protein 1 light chain 3 beta, is a crucial protein in the autophagy pathway. During autophagy, the cytosolic form of LC3 (LC3-I) is conjugated to phosphatidylethanolamine to form LC3-phosphatidylethanolamine conjugate (LC3-II), which localizes to autophagosomal membranes. Autophagy is essential for the degradation of cytoplasmic components, including cytosolic proteins and organelles, and is involved in maintaining cellular homeostasis [1].

In nonalcoholic steatohepatitis (NASH), impaired autophagy is implicated. In NASH-related studies, a decrease in the number of Map1lc3b puncta was associated with impaired autophagy, suggesting that Map1lc3b is involved in the pathogenesis of NASH [2]. In cardiac ischemia-reperfusion injury aggravated by particulate matter (PM) exposure, PM increased the expression of Map1lc3b, indicating its role in mitophagy and the subsequent cardiac injury. Treatment with adipose-derived stem cell exosomes (ADSC-Exos) containing Mir221 and Mir222, which target Map1lc3b, reduced cardiomyocyte mitophagy and apoptosis [3]. Also, in microglial activation induced by CKLF, Map1lc3b-II levels increased, suggesting autophagosome formation, but reduced mitophagy flux led to the accumulation of damaged mitochondria and microglial activation [4].

In conclusion, Map1lc3b is essential for autophagy and mitophagy processes. Studies using various models, including those related to NASH, cardiac ischemia-reperfusion injury, and microglial activation, have revealed its significance in disease-related biological processes. Understanding the role of Map1lc3b through these model-based research helps in uncovering disease mechanisms and may potentially lead to new therapeutic strategies for related diseases.

References:

1. Tanida, Isei, Ueno, Takashi, Kominami, Eiki. . LC3 and Autophagy. In Methods in molecular biology (Clifton, N.J.), 445, 77-88. doi:10.1007/978-1-59745-157-4_4. https://pubmed.ncbi.nlm.nih.gov/18425443/

2. Park, Hee-Seon, Song, Ji-Won, Park, Jin-Ho, Won, Young-Suk, Kwon, Hyo-Jung. 2020. TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation. In Autophagy, 17, 2549-2564. doi:10.1080/15548627.2020.1834711. https://pubmed.ncbi.nlm.nih.gov/33190588/

3. Lee, Tzu-Lin, Shen, Wen-Chi, Chen, Ya-Chun, Lee, Chiang-Wen, Chen, Yuh-Lien. 2024. Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway. In Autophagy, 21, 374-393. doi:10.1080/15548627.2024.2395799. https://pubmed.ncbi.nlm.nih.gov/39245438/

4. Wang, Hongyun, Ye, Junrui, Peng, Ye, Zhang, Zhao, Chen, Naihong. 2023. CKLF induces microglial activation via triggering defective mitophagy and mitochondrial dysfunction. In Autophagy, 20, 590-613. doi:10.1080/15548627.2023.2276639. https://pubmed.ncbi.nlm.nih.gov/37908119/