Phaf1-KO Mouse

Phaf1, also known as PHAF1/MYTHO (phagophore assembly factor 1/macro-autophagy and youth optimizer), is a novel autophagy regulator. Autophagy is crucial for maintaining muscle mass, function, and integrity, and Phaf1 is involved in this essential pathway [1].

In a study, downregulation of Phaf1 expression alleviated muscle atrophy triggered by fasting, denervation, cachexia, and sepsis. Prolonged Phaf1 downregulation led to a severe myopathic phenotype characterized by impaired autophagy, muscle weakness, myofiber degeneration, mTORC1 hyperactivation, and extensive ultrastructural defects. This phenotype was attenuated by the mTORC1 inhibitor rapamycin, positioning Phaf1 as a key regulator of skeletal muscle autophagy and tissue integrity [1]. Additionally, Phaf1 was highly upregulated in response to high-intensity exercise, emerging as a pivotal exercise-responsive autophagy marker positively associated with the LC3B-II:LC3B-I ratio [2]. In non-small cell lung cancer, the gene expression profile including Phaf1 could better predict the durable response to anti-PD-1/PD-L1 therapy [3]. In equine skeletal muscle, Phaf1 was identified as a potential candidate for skeletal muscle remodeling during high-intensity interval exercise with different rest periods [4].

In summary, Phaf1 is a significant gene involved in autophagy regulation, especially in maintaining skeletal muscle integrity. Its dysregulation can lead to muscle-related pathologies. Moreover, it shows potential as a predictive marker in non-small cell lung cancer immunotherapy and is associated with skeletal muscle remodeling during exercise. Studies on Phaf1 contribute to understanding autophagy-related biological processes and disease mechanisms.

References:

1. Franco-Romero, Anais, Leduc-Gaudet, Jean Philippe, Hussain, Sabah Na, Gouspillou, Gilles, Sandri, Marco. 2023. PHAF1/MYTHO is a novel autophagy regulator that controls muscle integrity. In Autophagy, 20, 965-967. doi:10.1080/15548627.2023.2224206. https://pubmed.ncbi.nlm.nih.gov/37309183/

2. Martinez-Canton, Miriam, Galvan-Alvarez, Victor, Gallego-Selles, Angel, Martin-Rincon, Marcos, Calbet, Jose A L. 2024. Activation of macroautophagy and chaperone-mediated autophagy in human skeletal muscle by high-intensity exercise in normoxia and hypoxia and after recovery with or without post-exercise ischemia. In Free radical biology & medicine, 222, 607-624. doi:10.1016/j.freeradbiomed.2024.07.012. https://pubmed.ncbi.nlm.nih.gov/39009244/

3. Zhang, Xiaoshen, Gao, Guanghui, Zhang, Qian, Luo, Heng, Zhou, Caicun. 2024. In-depth proteomic analysis identifies key gene signatures predicting therapeutic efficacy of anti-PD-1/PD-L1 monotherapy in non-small cell lung cancer. In Translational lung cancer research, 13, 34-45. doi:10.21037/tlcr-23-713. https://pubmed.ncbi.nlm.nih.gov/38405006/

4. Takahashi, Kenya, Mukai, Kazutaka, Takahashi, Yuji, Hatta, Hideo, Kitaoka, Yu. 2024. Comparison of long- and short-rest periods during high-intensity interval exercise on transcriptomic responses in equine skeletal muscle. In Physiological genomics, 57, 28-39. doi:10.1152/physiolgenomics.00066.2024. https://pubmed.ncbi.nlm.nih.gov/39661768/