Related Experiment Video
Updated: Jul 29, 2026
08:55
Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae
Published on: July 19, 2021
Mitochondrial Hsp70/MIM44 complex facilitates protein import
H C Schneider1, J Berthold, M F Bauer
1Institut für Physiologische Chemie der Universität München, Germany.
Nature
|October 27, 1994
Summary
Mitochondrial protein import relies on mitochondrial Hsp70 (heat shock protein 70) and MIM44. Their ATP-regulated complex acts as a molecular ratchet, driving protein translocation across mitochondrial membranes.
Area of Science:
- Mitochondrial biology
- Molecular chaperones
- Protein translocation
Background:
- Mitochondrial protein import is essential for cellular function.
- Mitochondrial Hsp70 (mt-Hsp70) is a key molecular chaperone in the mitochondrial matrix.
- MIM44 is an inner mitochondrial membrane component involved in protein import.
Purpose of the Study:
- To elucidate the mechanism of mt-Hsp70 recruitment and function in mitochondrial protein translocation.
- To investigate the role of MIM44 in facilitating protein import.
- To understand the regulation and energetics of the mt-Hsp70/MIM44 complex.
Main Methods:
- Investigating the interaction between mt-Hsp70 and MIM44.
- Analyzing the role of ATP in complex formation and function.
- Studying the sequential interaction of the complex with preproteins.
Main Results:
- MIM44 recruits mt-Hsp70 to the mitochondrial inner membrane import machinery.
- ATP regulates the formation of the mt-Hsp70/MIM44 complex.
- The complex sequentially interacts with unfolded preproteins, facilitating stepwise translocation.
- The translocation process is driven by ATP hydrolysis, acting as a molecular ratchet.
Conclusions:
- The mt-Hsp70/MIM44 complex is crucial for efficient protein translocation into mitochondria.
- ATP-dependent regulation and a molecular ratchet mechanism ensure vectorial protein movement.
- This study clarifies a fundamental process in mitochondrial protein import and molecular chaperone function.
Related Concept Videos
01:39Mitochondrial Protein Sorting
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
01:39Mitochondrial Precursor Proteins
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
Most of the mitochondrial precursors...
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:37Energy to Drive Translocation
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
01:34Protein Transport into the Inner Mitochondrial Membrane
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
01:32Export of Misfolded Proteins out of the ER
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...