mTOR

Question 1

Briefly describe what mTOR is

Answer 1

A kinase enzyme with two distinct protein complexes

• mTOR complex 1 (mTORC1 - primary nutrient-sensing complex) and 2 (mTORC2)
• these two complexes have different upstream inputs and downstream outputs
• phosphorylates things

Question 2

What are the five major inputs for mTORC1?

Answer 2

• AMINO ACIDS
• GROWTH FACTORS
• stress
• oxygen
• energy

Question 3

How does mTORC1 promotes cell growth?

Answer 3

Inducing anabolic and inhibiting metabolic processes

Question 4

Give five major outputs of mTORC1 activation

Answer 4

• PROTEIN SYNTHESIS
• Autophagy
• Inflammation
• LIPID SYNTHESIS
• GLYCOLYSIS

Question 5

How does mTORC1 promote protein synthesis?

Answer 5

2 Ways:
• phosphorylates protein so can initiate translation for amino acids
• phosphorylates ribosomal S6 kinase 1 (S6K1) which increases mRNA and ribosomal biogenesis

Question 6

How does mTORC1 induce lipogenesis?

Answer 6

• Activates SREBP-1 - a transcription factor that produces a lot of enzymes in the de novo lipogenesis pathway (ACC, FAS, SCD1)
• Activates PPAR-gamma - transcription factor which stimulates lipid uptake and lipogenesis (esp in adipose tissues)

Question 7

Briefly describe how mTORC1 can promote cancer development

Answer 7

mTOR1C activates transcription and translation of HIF-1a and other cell proliferation necessary for tumorigenesis

• Oncogenes promotes mTOR signalling pathway activation
• Tumor suppressors suppress mTOR signaling pathway activation

*mTOR is not the cause of cancer development, but is a consequence

Question 8

What is the link between mTOR activation and insulin resistance?

Answer 8

Chronic mTOR activation can induce insulin resistance

A high protein diet may put a lot of amino acids in the blood stream, which is why this diet could induce insulin resistance (AAs stimulate protein synthesis via activating mTORC1 signalling pathway)