MARIGOLD and MitoCIAO, two searchable compendia to visualize and functionalize protein complexes during mitochondrial
Giovanni Rigoni1, Enrique Calvo2, Christina Glytsou3
1Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy.
Cell Metabolism
|February 25, 2025
Summary
Researchers created two databases, MARIGOLD and MitoCIAO, to map dynamic mitochondrial protein complexes. These tools reveal how proteins assemble into complexes, aiding in understanding mitochondrial function and disease.
Area of Science:
- Mitochondrial biology
- Proteomics
- Systems biology
Background:
- Mitochondrial proteins form dynamic, high-molecular-weight complexes crucial for cellular functions.
- Understanding the dynamic assembly and interactions of these complexes is essential for elucidating mitochondrial roles.
- Existing databases lack comprehensive data on dynamic mitochondrial complex remodeling.
Purpose of the Study:
- To generate and validate searchable compendia of mitochondrial protein complexes.
- To elucidate the dynamic distribution of proteins within complexes during mitochondrial remodeling.
- To develop a tool for predicting protein co-occurrence and functionalizing mitochondrial complexes.
Main Methods:
- Proteins within mitochondrial complexes were identified using mass spectrometry after blue-native gel electrophoresis.
- Mitochondria were analyzed in unperturbed, remodeled, and permeabilized states.
- The MARIGOLD database (627 proteins) and MitoCIAO interactome tool were developed using statistical correlation.
Main Results:
- MARIGOLD provides insights into dynamic protein distribution within complexes during mitochondrial membrane remodeling.
- MitoCIAO successfully predicted validated interactions within the mitochondrial cristae organization system (MICOS) and optic atrophy 1 (OPA1) complexes.
- MitoCIAO facilitated the functionalization of ATPase family AAA domain-containing 3A (ATAD3A) complexes with OPA1 and ribosomal proteins.
Conclusions:
- The developed compendia reveal the dynamic nature of mitochondrial protein complexes.
- MARIGOLD and MitoCIAO enable the functional characterization of mitochondrial complexes.
- These resources advance the study of mitochondrial structure, function, and disease mechanisms.
Keywords:
ATAD3AOPA1cristae remodelinginteractomemitochondriamitochondrial complexesmitoribosome stabilityMore Related Videos
10:45A Faster, High Resolution, mtPA-GFP-based Mitochondrial Fusion Assay Acquiring Kinetic Data of Multiple Cells in Parallel Using Confocal Microscopy
Published on: July 20, 2012
16.5K
08:33Author Spotlight: An Optimized Automated Method for Investigating Retinoic Acid Receptors in Neuronal Mitochondria
Published on: July 28, 2023
556
Related Concept Videos
01:19Translocation of Proteins into the Mitochondria
3.0K
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,...
3.0K
01:21Structure of Porins
2.9K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
2.9K
01:39Mitochondrial Protein Sorting
4.2K
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...
4.2K
01:39Mitochondrial Precursor Proteins
2.5K
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...
Most of the mitochondrial...
2.5K
01:28The Inner Mitochondrial Membrane
3.2K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.2K
01:12Porin Insertion in the Outer Mitochondrial Membrane
2.8K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
2.8K