Structural basis of respiratory complex adaptation to cold temperatures

Area of Science:

• Biochemistry
• Structural Biology
• Mammalian Physiology

Background:

• Mammals activate brown fat for thermogenesis in response to cold.
• This process relies on the electron transport chain but lacks structural understanding of respiratory complex adaptation.

Purpose of the Study:

• To elucidate the structural basis of respiratory supercomplex adaptation in brown fat during cold exposure.
• To understand the dynamics and mechanisms of enhanced respiratory capacity.

Main Methods:

• Combined thermoregulatory physiology, cryoelectron microscopy (cryo-EM), and multiscale simulations.
• Studied endogenous respiratory supercomplexes from mice at different temperatures.
• Analyzed lipid-protein arrangements and catalytic states.

Main Results:

• Identified a cold-induced conformation (type 2) of the CI:III2 supercomplex with altered CIII2 orientation.
• Observed shortened inter-complex Q exchange space favoring electron transfer.
• Simulations revealed lipid-protein interactions stabilizing the type 2 complex for enhanced catalytic activity.

Conclusions:

• Unveiled the structural and energetic mechanisms of increased respiratory capacity in brown fat during cold.
• Demonstrated how supercomplex dynamics contribute to thermoregulation at a molecular level.