Table 3.

Switches that mediate the functional transitions of autophagy.

Disease/Mold	Switches	Conversion of autophagy function	Citation
Insulin withdrawal	VCP, calpain 1 and calpain 2	ACD was induced by insulin withdrawal. The overexpression of VCP, calpain 1 and calpain 2 converted the cell death pattern to apoptosis	[26, 176]
I/R	–	Treatment with 3-MA for 20 min before hypoxic ischemia induction inhibited autophagy and increased the neuronal death rate. However, when 3-MA was used 4 hours after ischemia, it significantly reduced lesion formation.	[183]
I/R	AMPK	Ischemia induced AMPK activation and protective autophagy in the myocardium. Lethal autophagy was activated by Beclin1-dependent and AMPK-independent autophagy during the reperfusion phase	[184]
Amyotrophic lateral sclerosis	–	Autophagy defects in motor neurons caused denervation of the tibialis anterior muscle and episodes of hindlimb tremor in the early stages of the disease. However, the autophagy defect alleviated glial inflammation and blocked the activation of interneuron c-Jun at the late stage, extending the lifespan of the mice.	[185]
Virus infection	–	Autophagy in tick-borne encephalitis virus-infected macrophages was altered with an increasing duration of infection. In the early stages of infection, autophagy inhibited viral replication. In contrast, autophagy inhibited antiviral responses by limiting IFN-β production in the later stages of infection.	[186]
Rheumatoid arthritis	–	Osteoarthritic synovial fibroblasts were treated with an ER stress inducer and a proteasome inhibitor to activate autophagy. The former induced autophagy-mediated nonapoptotic cell death, whereas the latter induced protective autophagy to inhibit apoptosis.	[187]
OA	SIRT1	Autophagy selectively cleared SIRT1 to increase LOX-1 expression, leading to chondrocyte death. In contrast, under physiological conditions, SIRT1 is normally expressed induces autophagy.	[188]