I am asking about autophagy inducers and inhibitors for use in mammalian ovaries in vitro as well as in vivo condition.
Hello Pramod Kumar Yadav
Autophagy is a complex process involving many players. Constitutive autophagy helps prevent unwanted and unnecessary increase in cell mass thereby contributing to cell homeostasis. Autophagy can also be transitorily hyper-induced for instance, to meet the need to recover from nutrient or energy depletion.
An inducer of autophagy inhibits molecules that are involved in the negative regulation of autophagy. mTOR, a member of the PI3K family, is an important regulator of multiple intracellular processes that include protein translation as well as autophagy and metabolism in response to different nutrient, energy, and growth factor–signalling conditions. mTOR is a major negative regulatory axis of autophagy. Thus, direct inhibitors of mTOR and those of pathways activating mTOR may be used to induce autophagy. For instance, Rapamycin is an mTOR inhibitor which is an autophagy inducer.
Also, autophagy is negatively regulated by class I PI3K. Targeting this class I PI3K with inhibitors such as CH5132799, GDC-0980, and GDC-0941, leads to the activation of autophagy.
An inhibitor of autophagy inhibits molecules that are involved in the positive regulation of autophagy. Autophagy is positively regulated by PI3P, the product of class III PI3K (VPS34 complexes).
3-Methyladenine (3-MA) and LY294002 have been widely used as inhibitors of class III PI3K to block autophagosome formation.
I hope this helps.
Best.
Hi Pramod Kumar Yadav ,
if you are new to the field, I recommend to have a look at the community-approved guidelines published by Klionsky et al. (10.1080/15548627.2020.1797280).
In chapter C, section 2, you will find a nice paragraph called "Autophagy inhibitors and inducers". I am pretty sure this will answer many questions. Also helpful for a quick overview: Table 2 from Rubinsztein et al. (10.1038/nrd2272).
Personally, i used serum starvation in order to induce autohagy in vitro, and wortmannin or pepstatin A/E-64d as inhibitors, depending on which step you want to inhibit. Inhibitors are necessary in order to investigate full autophagic flux.
Good luck - CL
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