A new study sheds light on the organization of proteins within mitochondria.
Mitochondria, the “powerhouses” of cells, play a crucial role in the energy production of organisms and are involved in various metabolic and signaling processes. Researchers from the University Hospital Bonn and the University of Freiburg have now gained a systematic understanding of the organization of proteins within mitochondria.
The protein map of mitochondria represents a critical foundation for further exploring the functions of these cellular powerhouses, and holds implications for disease understanding. The new research has recently been published in the prestigious journal Nature.
Mitochondria are essential components of cells and are surrounded by a double membrane that separates them from the rest of the cell. They produce the majority of the energy needed to sustain these activities. Beyond energy production, mitochondria play key roles in metabolism and signaling, serving as a surface for inflammation processes and programmed cell death.
Model of the quality control mechanism for removing arrested proteins from the mitochondrial entry gate. Credit: Schulte et al., 2023 Nature
Defects in mitochondria lead to numerous diseases, especially of the nervous system. Therefore, the molecular understanding of mitochondrial processes is of the highest relevance for basic medical research. The molecular workers in the cell are usually proteins.
Mitochondria can contain around 1,000 or more different proteins. To execute functions, several of these molecules often work together and form a protein machine, also called a protein complex. Proteins also interact in the execution and regulation of molecular processes. Yet little is known about the organization of mitochondrial proteins in such complexes.
Precision in the analysis of dynamic protein machines
The research groups of Prof. Thomas Becker and Dr. Fabian den Brave at the UKB, together with the research groups of Prof. Bernd Fakler, Dr. Uwe Schulte, and Prof. Nikolaus Pfanner at the University of Freiburg, have created a high-resolution image of the organization of proteins in protein complexes, known as MitCOM. This involved a specific method known as complexome profiling to record the fingerprints of individual proteins at an unprecedented resolution.
MitCOM reveals the organization into protein complexes of more than 90 percent of the mitochondrial proteins from baker’s yeast. This allows to the identification of new protein-protein interactions and protein complexes – important information for further studies.
Quality control in the mitochondrial entry gate TOM as an example
Researchers at UKB in cooperation with Collaborative Research Center 1218 “Regulation of cellular function by mitochondria,” have shown how this dataset can be used to elucidate new processes. Mitochondria import 99 percent of their proteins from the liquid portion of the cell, known as cytosol. In this process, a protein machinery called the TOM complex enables the uptake of these proteins through the membrane into the mitochondria.
However, it is largely unclear how proteins are removed from the TOM complex when they get stuck during the transport process. To elucidate this, the team led by Prof. Becker and Dr. den Brave used information from the MitCOM dataset. It was shown that non-imported proteins are specifically tagged for cellular degradation.
Research by Ph.D. student Arushi Gupta further revealed a pathway by which these tagged proteins are subsequently targeted for degradation. Understanding these processes is important because defects in protein import can lead to cellular damage and neurological diseases.
“The example from our study demonstrates the great potential of the MitCOM dataset to elucidate new mechanisms and pathways. Thus, this map of proteins represents an important source of information for further studies that will help us to understand the functions and origin of the cell’s powerhouse,” says Prof. Becker, director of the Institute of Biochemistry and Molecular Biology at UKB.

News
Nano-Enhanced Hydrogel Strategies for Cartilage Repair
A recent article in Engineering describes the development of a protein-based nanocomposite hydrogel designed to deliver two therapeutic agents—dexamethasone (Dex) and kartogenin (KGN)—to support cartilage repair. The hydrogel is engineered to modulate immune responses and promote [...]
New Cancer Drug Blocks Tumors Without Debilitating Side Effects
A new drug targets RAS-PI3Kα pathways without harmful side effects. It was developed using high-performance computing and AI. A new cancer drug candidate, developed through a collaboration between Lawrence Livermore National Laboratory (LLNL), BridgeBio Oncology [...]
Scientists Are Pretty Close to Replicating the First Thing That Ever Lived
For 400 million years, a leading hypothesis claims, Earth was an “RNA World,” meaning that life must’ve first replicated from RNA before the arrival of proteins and DNA. Unfortunately, scientists have failed to find [...]
Why ‘Peniaphobia’ Is Exploding Among Young People (And Why We Should Be Concerned)
An insidious illness is taking hold among a growing proportion of young people. Little known to the general public, peniaphobia—the fear of becoming poor—is gaining ground among teens and young adults. Discover the causes [...]
Team finds flawed data in recent study relevant to coronavirus antiviral development
The COVID pandemic illustrated how urgently we need antiviral medications capable of treating coronavirus infections. To aid this effort, researchers quickly homed in on part of SARS-CoV-2's molecular structure known as the NiRAN domain—an [...]
Drug-Coated Neural Implants Reduce Immune Rejection
Summary: A new study shows that coating neural prosthetic implants with the anti-inflammatory drug dexamethasone helps reduce the body’s immune response and scar tissue formation. This strategy enhances the long-term performance and stability of electrodes [...]
Scientists discover cancer-fighting bacteria that ‘soak up’ forever chemicals in the body
A family of healthy bacteria may help 'soak up' toxic forever chemicals in the body, warding off their cancerous effects. Forever chemicals, also known as PFAS (per- and polyfluoroalkyl substances), are toxic chemicals that [...]
Johns Hopkins Researchers Uncover a New Way To Kill Cancer Cells
A new study reveals that blocking ribosomal RNA production rewires cancer cell behavior and could help treat genetically unstable tumors. Researchers at the Johns Hopkins Kimmel Cancer Center and the Department of Radiation Oncology and Molecular [...]
AI matches doctors in mapping lung tumors for radiation therapy
In radiation therapy, precision can save lives. Oncologists must carefully map the size and location of a tumor before delivering high-dose radiation to destroy cancer cells while sparing healthy tissue. But this process, called [...]
Scientists Finally “See” Key Protein That Controls Inflammation
Researchers used advanced microscopy to uncover important protein structures. For the first time, two important protein structures in the human body are being visualized, thanks in part to cutting-edge technology at the University of [...]
AI tool detects 9 types of dementia from a single brain scan
Mayo Clinic researchers have developed a new artificial intelligence (AI) tool that helps clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using a single, widely available scan—a transformative [...]
Is plastic packaging putting more than just food on your plate?
New research reveals that common food packaging and utensils can shed microscopic plastics into our food, prompting urgent calls for stricter testing and updated regulations to protect public health. Beyond microplastics: The analysis intentionally [...]
Aging Spreads Through the Bloodstream
Summary: New research reveals that aging isn’t just a local cellular process—it can spread throughout the body via the bloodstream. A redox-sensitive protein called ReHMGB1, secreted by senescent cells, was found to trigger aging features [...]
AI and nanomedicine find rare biomarkers for prostrate cancer and atherosclerosis
Imagine a stadium packed with 75,000 fans, all wearing green and white jerseys—except one person in a solid green shirt. Finding that person would be tough. That's how hard it is for scientists to [...]
Are Pesticides Breeding the Next Pandemic? Experts Warn of Fungal Superbugs
Fungicides used in agriculture have been linked to an increase in resistance to antifungal drugs in both humans and animals. Fungal infections are on the rise, and two UC Davis infectious disease experts, Dr. George Thompson [...]
Scientists Crack the 500-Million-Year-Old Code That Controls Your Immune System
A collaborative team from Penn Medicine and Penn Engineering has uncovered the mathematical principles behind a 500-million-year-old protein network that determines whether foreign materials are recognized as friend or foe. How does your body [...]