Angiotensin II decreases autophagy and recruits double FYVE domain-containing protein 1 in the mitochondria of vascular smooth muscle cells

Autophagy, an intracellular degradation process crucial for maintaining cellular homeostasis, is regulated by angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs). However, the role of Double FYVE Domain Containing Protein 1 (DFCP1), an early autophagosome protein that inhibits autophagy, particularly in VSMCs, is still largely unknown. We investigated the role of DFCP1 on Ang II-mediated autophagy in VSMCs and found that Ang II (100 nM) decreased beclin-1 and LC3II (a late autophagosome maker) protein expressions. The Ang II-mediated decrease in beclin-1 and LC3-II was attenuated by an AT 1 R antagonist, losartan (10 µM), indicating that Ang II decreased autophagy in the autophagosome formation stage through AT 1 R. Ang II had no effect on the protein expression of Unc-51-like autophagy activating kinase 1 (ULK1) and phospho-ULK1, which are important in the early stages of autophagosome formation. By contrast, Ang II increased DFCP1 and decreased LC3 protein expressions in a concentration (10 nM-1 mM) and time-dependent manner. Ang II (1 nM, 15 min) increased the DFCP1 puncta fluorescence intensity and the colocalization of DFCP1 with Hsp60 (Veh: 5.7±3.1% vs. Ang II: 11.6±6.7%, N=5, p<0.05, Student’s t -test), a heat shock chaperonin in mitochondria that plays a critical role in mitochondria dynamics and homeostasis. We conclude that in VSMCs, Ang II increases DFCP1 protein expression and decreases non-selective autophagy, which is associated with the initiation of mitophagy, a subtype of selective autophagy. National Institutes of Health DK119652 and DK134574. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.