Exercise Physiology | mTORC1 and Muscle Protein Synthesis

Summary

In this Catalyst University exercise physiology video, Kevin discusses the critical role of the mTOR protein complex in skeletal muscle hypertrophy and myofibril agenesis. He explains how mTOR activation is essential for muscle protein synthesis, which is crucial for muscle growth and strength. The video delves into the complex's activation by amino acids, particularly leucine, and how it influences muscle protein synthesis and inhibits protein degradation. It also touches on the role of other factors like glucose and growth factors in mTOR activation.

Takeaways

• 💪 The video discusses the importance of the mTOR (mammalian Target of Rapamycin) protein complex for muscle protein synthesis, which is crucial for muscle growth and strength.
• 🏋️‍♂️ mTOR is inactive without amino acids, particularly branched-chain amino acids (BCAAs), which are essential for its activation and muscle hypertrophy.
• 🔄 mTOR moves from the Golgi apparatus to the lysosome membrane to become active, a process stimulated by amino acids, especially serine and glutamine.
• 🍽️ The presence of BCAAs, notably leucine, inhibits Susteren 2, which in turn activates Gator-2, leading to mTOR activation and muscle protein synthesis.
• 🧬 The Rag proteins, which are G proteins, play a key role in mTOR activation. They are activated by amino acids and bind to mTOR, contributing to its full activation.
• 🔑 The presence of arginine, another amino acid, inhibits tSC1 and tSC2, leading to the activation of Reb, which is necessary for mTOR activation.
• 📈 mTOR activation is a multi-step process requiring the presence of amino acids, active Rag GTPases, and active Reb.
• 🚫 mTOR not only stimulates protein synthesis but also inhibits autophagy and protein degradation, which are essential for muscle growth.
• 💊 Beta-hydroxy beta-methylbutyrate (HMB), an ergogenic aid, functions similarly to BCAAs in stimulating mTOR and promoting muscle protein synthesis.
• 🔗 Other factors such as glucose and growth factors also stimulate mTOR, highlighting the complexity of muscle protein synthesis regulation.

Q & A

What is the primary function of mTORC1 in muscle growth?

mTORC1 is crucial for muscle protein synthesis, which is essential for muscle hypertrophy or the growth of skeletal muscles.

Why is muscle protein synthesis necessary for muscle hypertrophy?

Muscle protein synthesis is necessary for muscle hypertrophy because it leads to the production of new muscle proteins, which in turn increases muscle size and strength.

What role do amino acids play in the activation of mTORC1?

Amino acids are essential for the activation of mTORC1 as they act as sensors that stimulate the translocation of mTORC1 from the Golgi apparatus to the lysosome, where it can be activated.

How do the amino acids serine and glutamine specifically contribute to mTORC1 activation?

Serine and glutamine are particularly important amino acids for mTORC1 activation because they bind to proteins on the Golgi body that act as amino acid sensors, triggering the translocation and activation of mTORC1.

What is the significance of the presence of BCAAs, especially leucine, in the activation of mTORC1?

Branched-chain amino acids (BCAAs), particularly leucine, are significant because they inhibit the inhibition of GATOR2, leading to the activation of GATOR1 and subsequently the activation of Rag proteins, which are crucial for mTORC1 activation.

Can you explain the role of the Rag proteins in mTORC1 activation?

The Rag proteins become activated when GATOR1 is active, and they physically bind to the Raptor component of mTORC1, contributing to its activation. They require specific guanine nucleotide bindings (GTP for RagAB and GDP for RagCD) for optimal function.

What is the function of the vacuolar ATPase (v-ATPase) in the activation of mTORC1?

The vacuolar ATPase (v-ATPase) spans the lysosome membrane and, with the help of a transporter, can further activate Rag proteins when amino acids are sufficiently present inside the lysosome, leading to a two-fold activation of Rag GTPases.

How does arginine contribute to mTORC1 activation?

Arginine inhibits TSC1 and TSC2, which are proteins that normally inhibit Rheb. By inhibiting TSC1 and TSC2, arginine allows Rheb to become active, which in turn activates mTORC1.

What are the three key events necessary for the maximal activation of mTORC1?

The three key events necessary for the maximal activation of mTORC1 are: 1) translocation of mTORC1 to the lysosome, 2) activation of Rag GTPases through GATOR2 and the presence of general amino acids, and 3) activation of Rheb when arginine is present.

How does mTORC1 stimulate muscle protein synthesis?

mTORC1 stimulates muscle protein synthesis by directly phosphorylating proteins like 4E-BP1 and p70S6K, which promote the initiation and elongation of protein synthesis.

What is the role of HMB (beta-hydroxy beta-methylbutyrate) in muscle protein synthesis?

HMB acts similarly to leucine and other BCAAs by inhibiting Susteren, leading to the activation of Gator2 and mTORC1, thus promoting muscle protein synthesis.