Figure 3.

Klotho regulates cell death. Klotho regulates autophagic flux through PI3K/AKT/mTOR, MAPK, and AMPK pathways. Klotho can increase the binding of Beclin-1 to Bcl-2, reduce Beclin-1’s interaction with other autophagy-related proteins, and thereby regulate autophagy. Additionally, Klotho indirectly upregulates autophagy by inhibiting the activity of NLRP3 inflammatory vesicles, which helps prevent renal tubular cell death. Klotho also indirectly regulates autophagy by controlling the excretion of Pi. PI3K, phosphoinositide 3-kinase; AKT, protein kinase B; mTOR, mammalian target of rapamycin; MAPK, mitogen-activated protein kinase; AMPK, adenosine monophosphate-activated protein kinase; NLRP3, nucleotide-binding oligomerization domain-like pyrin domain-containing protein 3; PiT, phosphate transporter.