# Muscle biopsies from two ISS astronauts revealed major mitochondrial protein losses while different exercise levels tracked how much strength each person preserved

> Six months in orbit left a deep molecular mark inside the leg muscles of two astronauts. After they returned from the International Space Station, researchers found steep declines in proteins that help muscle cells produce energy. The changes involved the tiny power-producing...

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Published: 2026-08-22T11:00:02+00:00
Categories: Explainer, Space

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Six months in orbit left a deep molecular mark inside the leg muscles of two astronauts. After they returned from the **International Space Station**, researchers found steep declines in proteins that help muscle cells produce energy. The changes involved the tiny power-producing structures known as mitochondria, which support movement and help muscle fibers remain healthy.

The findings come from a [study in npj Microgravity](https://www.nature.com/articles/s41526-024-00406-3) published on June 5, 2024. Led by **Marta Murgia** and colleagues, the research examined muscle samples collected before flight, on the day of landing and two weeks after the astronauts returned to Earth.

The astronauts showed several shared changes, yet their responses also differed. One exercised about 50 percent more during the mission and preserved more muscle mass and force, according to earlier measurements. The protein results suggest that exercise may also support some parts of the cell's energy machinery, although a study of two people cannot prove cause and effect.

## How researchers tracked muscle changes

Human muscle is built from thousands of proteins with different jobs. Some allow fibers to contract, while others move fuel through the cell or help repair damage. The complete set of proteins measured in a sample is called its **skeletal muscle proteome**. Changes in protein abundance can reveal processes that remain hidden during routine medical exams.

The research team studied six biopsies from the astronauts' **soleus muscle**, a lower-leg muscle that helps people stand upright on Earth. Gravity keeps this muscle active through much of the day. In orbit, the body no longer needs the same steady effort to support its weight, so the soleus is especially vulnerable to reduced use.

Samples were collected at three points: before the mission, on the day of landing and 14 days later. Scientists used **mass spectrometry**, a laboratory method that identifies molecules according to their mass and electrical behavior. Each biopsy was measured several times to improve the precision of the protein estimates. The [open-access study](https://pmc.ncbi.nlm.nih.gov/articles/PMC11153545/) describes the sampling and analysis in detail.

Researchers then compared the abundance of proteins at each stage. Their calculations separated the mission time points for both astronauts, although the two people had large biological differences before and after flight. Such personal variation is common in muscle research and can influence how strongly someone responds to inactivity.

## Mitochondrial proteins fell after spaceflight

The strongest shared signal involved **mitochondria**, structures that release usable energy from food. Muscle cells need large numbers of them because movement requires a constant energy supply. The soleus contains many mitochondria since it normally performs long periods of low-level work.

Many of the falling proteins belonged to oxidative phosphorylation, often shortened to OXPHOS. During **oxidative phosphorylation**, groups of proteins pass electrons through the inner mitochondrial membrane. The process builds the conditions needed to produce ATP, the small energy-carrying molecule used by cells.

According to the paper, the astronauts lost 43 percent and 55 percent of the total OXPHOS protein complement measured during the mission. Proteins in the mitochondrial matrix, the inner space of the organelle, also declined. The researchers described a dramatic net decrease in mitochondrial volume, mitochondrial number or both across the two astronauts.

The team used **MitoCarta3.0**, a scientific catalog of mitochondrial proteins, to classify the results. It identified 796 such proteins in the samples, representing about 73 percent of the catalog's known mitochondrial proteome. The broad coverage allowed researchers to see changes across several parts of the organelle instead of relying on a small group of markers.

## The two astronauts responded differently

Individual biology remained a major part of the results. When the researchers compared the complete protein profiles, differences between the astronauts could be larger than the changes recorded across the mission. Their muscles also had somewhat different mixtures of fiber types, which may have influenced their starting protein levels.

Astronaut B completed about 50 percent more exercise than astronaut A during the six-month stay. Earlier work found greater losses of muscle fiber size and force in astronaut A. The protein analysis followed a similar general direction, with astronaut A often showing larger declines in proteins linked to the mitochondrial respiratory chain and the citric acid cycle, which helps cells process fuel.

Some proteins connected with antioxidant defenses and cellular cleanup moved in opposite directions between the astronauts. Such variation could reflect exercise levels, natural biological differences or other features of life in orbit. With only two participants, the study cannot separate those influences with statistical confidence.

## Exercise may protect cellular power systems

Exercise aboard the ISS uses specialized equipment that can create resistance without relying on gravity. Astronauts run with restraints on a treadmill, pedal a cycle machine and perform resistance movements. These sessions place mechanical loads on muscles that would otherwise perform far less work in orbit.

Greater activity appeared to support the preservation of several mitochondrial proteins in astronaut B. Exercise also correlated with proteins involved in **autophagy**, the process cells use to break down worn or damaged components. Healthy autophagy can remove faulty mitochondria before they interfere with energy production.

Antioxidant proteins offered another possible clue. Catalase, an enzyme that helps clear hydrogen peroxide, rose more than fourfold in astronaut B on the day of landing, while astronaut A showed little change. Peroxiredoxin 2, another antioxidant enzyme, also followed a pattern that appeared to track the astronauts' different exercise levels.

The association suggests two possible benefits from physical activity. Mechanical loading directly tells muscle fibers to maintain their structure, while exercise-related antioxidant responses may give mitochondria added protection. The protein measurements support both possibilities, although larger studies will be needed to test them separately.

## Oxidative stress could deepen muscle damage

Reduced muscle use is a familiar problem on Earth. Bed rest, limb immobilization and serious illness can quickly weaken muscles because fibers receive fewer signals to maintain their size. Ground studies often reproduce part of the muscle loss seen during spaceflight, yet mitochondrial protein declines on Earth can be slower or smaller over similar periods.

The authors propose that **reactive oxygen species** may help explain the stronger mitochondrial signal in orbit. These chemically active molecules are produced during normal cell activity. In controlled amounts, they help carry useful signals. Excess production can damage proteins, cell membranes and genetic material.

Spaceflight combines reduced mechanical loading with increased exposure to ionizing radiation. Radiation may add to oxidative pressure inside cells, while inactivity changes how mitochondria operate and how muscles control antioxidant defenses. The study did not measure the exact source of the damaging molecules, so the proposed role of radiation remains a hypothesis for future experiments.

## The limits of a two-astronaut study

Two participants provide a rare view of human tissue after long-duration spaceflight, but the small sample places firm limits on the conclusions. Astronaut studies often involve very few people because crews are small, mission schedules are demanding and muscle biopsies are invasive. Technical repeats make each laboratory measurement more reliable, yet they do not increase the number of individual humans studied.

The research also focused on the soleus. Other muscles contain different fiber mixtures and perform different tasks, so they may respond differently. Muscles used for quick, powerful movements could show another pattern from a slow, endurance-focused muscle that normally supports posture.

Biopsies taken on landing day record the combined result of six months in space and the first hours of renewed gravity. They cannot reveal exactly when each protein began to fall. In-flight samples would provide a clearer timeline, although collecting muscle tissue during a mission would create medical and operational challenges.

Personal factors may also affect the response. Exercise history, metabolism and natural differences in muscle composition can change how an individual adapts to unloading. The [University of Padova](https://www.research.unipd.it/handle/11577/3514901) research record lists the study's international team, which also included scientists connected with the **German Aerospace Center** and several European research institutions.

## What the findings mean for Mars missions

Future **Mars missions** could expose crews to reduced gravity and space radiation for far longer than a typical ISS stay. Astronauts would also need enough strength to work after landing, when they may have to leave their spacecraft, handle equipment and respond to emergencies without immediate help from Earth.

Exercise will remain a central defense, yet the findings suggest that training plans may need to protect mitochondrial health as well as muscle size. Researchers could monitor antioxidant proteins, energy metabolism and cellular cleanup pathways to identify astronauts who are losing protection faster than expected. Exercise programs might then be adjusted for each crew member.

Larger astronaut studies, tissue-chip experiments and carefully designed ground simulations can test whether oxidative stress drives the mitochondrial decline. The [archived research paper](https://elib.dlr.de/215170/1/s41526-024-00406-3%20%282%29.pdf) also points toward measurements that could track mitochondrial health during flight. Better monitoring may help mission doctors detect muscle changes before they become severe, giving future crews a stronger chance of arriving at another world ready to work. Broader mission context is available from [NASA's Human Research Program](https://www.nasa.gov/hrp/).