A new look at more than two decades’ worth of archival data from NASA’s Spirit mission suggests that the Martian soil may hold iron-bearing minerals -- hematite and altered magnetite -- that were too faint for scientists to detect in real time during the mission.

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University of Michigan Rogel Cancer Center researchers have unveiled a groundbreaking metabolic mechanism that colorectal cancer cells exploit to maintain exceptionally high iron levels, a discovery that opens promising avenues for targeted cancer therapies. Published recently in Cell Metabolism, this study provides an unprecedented insight into how tumor cells sidestep iron toxicity and evade a form of cell death known as ferroptosis, potentially revolutionizing the understanding of metal metabolism in cancer biology.

Colorectal cancer cells are known to harbor elevated iron concentrations, far surpassing those found in healthy cells. Iron is a double-edged sword in cellular physiology—essential for processes like DNA synthesis and cell proliferation but lethal in excess due to its propensity to generate harmful reactive oxygen species. Ordinarily, cells with excessive iron succumb to ferroptosis, a specialized form of oxidative cell death driven by iron-mediated lipid peroxidation. Tumor cells subvert this natural safeguard, sustaining iron overload without triggering their own demise, but how they achieve this has remained elusive—until now.

The investigative team led by Dr. Yatrik Shah, Horace W. Davenport Collegiate Professor of Physiology at Michigan Medicine, employed a metabolism-directed CRISPR screening approach to systematically dissect the pathways protecting colorectal cancer cells from iron-induced oxidative damage. Surprisingly, canonical ferroptotic enzymes, previously presumed central to this resistance, were found non-essential for tumor survival. This redirected focus led the scientists to explore mitochondrial metabolism more profoundly.

Their research unveiled that the mitochondrial enzyme complex II plays a pivotal role in safeguarding cancer cells from iron-induced toxicity. Complex II regulates coenzyme Q (CoQ) within mitochondria, a key antioxidant molecule that quells oxidative stress. By fine-tuning CoQ’s redox state, complex II effectively buffers the destructive potential of accumulated iron, preventing ferroptosis and enabling cancer cell proliferation. When researchers knocked out complex II in colorectal cancer models, iron toxicity became unmanageable for the tumor cells, leading to widespread cell death and marked tumor growth inhibition.

Crucially, complex II’s protective mechanism appears specific to the high-iron environment of cancer cells. In mouse models, disruption of complex II elicited negligible adverse effects on normal tissues, underscoring the therapeutic potential of selectively targeting this mitochondrial axis in colorectal cancer. This specificity addresses a significant hurdle in oncology: minimizing treatment toxicity while maximizing antitumor efficacy.

Further intricacies emerged as the study revealed a feedback loop wherein iron itself modulates complex II activity, suggesting a sophisticated regulatory axis that maintains iron homeostasis within tumors. This bidirectional interaction offers additional molecular targets for disrupting iron tolerance in cancer cells and deepening our understanding of tumor metabolism.

These findings represent a paradigm shift from earlier hypotheses centered on canonical ferroptosis regulators, highlighting the necessity of focusing on mitochondrial metabolism in cancer research. By leveraging sophisticated genome-editing tools and bioenergetic profiling, the Rogel Cancer Center team charted a novel course for drug discovery efforts aimed at crippling iron addiction—a hallmark of not only colorectal but potentially many other malignancies.

The next phase of this research endeavors to identify and develop potent inhibitors of complex II or its associated metabolic pathways. Given that dysregulated iron metabolism is a common vulnerability across diverse cancer types, these interventions could herald a new era of broad-spectrum anticancer strategies. Moreover, detailed characterization of iron complex II interplay might uncover additional metabolic dependencies exploitable for therapeutic gains.

This transformative research underscores the intricate metabolic adaptations that empower colorectal cancers to circumvent intrinsic iron toxicity constraints. By illuminating the heme-complex II axis as a linchpin in maintaining oxidative balance amid iron overload, it offers a highly selective target for the design of next-generation anticancer agents.

Researchers anticipate that combining complex II inhibition with other therapies may amplify treatment responses and overcome resistance mechanisms. As the quest to outsmart cancer evolves, this study reinforces the vital role of mitochondrial metabolism understanding in crafting innovative clinical interventions.

In sum, the University of Michigan team’s discovery of complex II’s role in buffering iron toxicity not only deciphers a long-standing biological enigma but also charts a compelling translational pathway. It epitomizes how fundamental metabolic insights can accelerate the development of precision treatments conferring hope to millions affected by colorectal cancer worldwide.

Subject of Research: Cells
Article Title: Iron addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death
News Publication Date: June 17, 2026
Web References: http://dx.doi.org/10.1016/j.cmet.2026.04.020
References: “Iron addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death,” Cell Metabolism, DOI: 10.1016/j.cmet.2026.04.020
Image Credits: Shah Lab, Rogel Cancer Center
Keywords: Colorectal cancer, iron metabolism, ferroptosis, complex II, coenzyme Q, mitochondrial metabolism, oxidative cell death, tumor metabolism, cancer therapy

An iron artifact recovered by archaeologists may be the oldest of its kind ever found in Japan, according to new research.

Recovered during excavations at the Hayashi-Fujishima archaeological site in Fukui, the capital city of Fukui Prefecture, the artifact measures slightly more than an inch and a half across, just under an inch in width, and just a millimeter in thickness.

The presence of tiny, triangular teeth measuring up to 3 millimeters deep indicates the artifact’s use as an early saw, according to investigations by the Fukui Prefectural Archaeological Research Center, which recently announced the discovery.

While similar discoveries have been made in Japan, none are believed to be as old as this saw, which archaeologists have tentatively dated to the late Yayoi Pottery Culture Period, which thrived between the second and third centuries, making it the oldest known in the country.

Tomokatsu Uozu, Deputy Director at the Center, said the age of the discovery indicates the advancement of early iron technologies along the region’s coastal communities during the period.

“The artifact could be an important piece of evidence supporting the advancement of ironware culture along the Sea of Japan coast during the Yayoi period,” Uozu recently told The Asahi Shimbun.

Similar Discoveries in the Ancient East

The saw uncovered at the Hayashi-Fujishima archaeological site bears some similarities to saws from the same period that have been unearthed during past excavations in China.

Such similarities are important, since it is believed that the same iron processing techniques used in the creation of the saw from the Hayashi-Fujishima site originated in China, having been carried across the Korean Peninsula and eventually reaching northern Kyushu, where ancient traders carried it along the Sea of Japan to its eventual arrival at Fukui.

The saw recently showcased by the Fukui Prefectural Archaeological Research Center is only one example of the many artifacts recovered from the Hayashi-Fujishima site.

Identified Decades After Its Discovery

Past work at the site has uncovered additional iron artifacts, as well as stone tools, pottery, distinctive “magatama” and “kudatama” bead varieties, and a range of items during primary excavations, which were conducted during the late 1990s and early 2000s.

The site is believed to also host what remains of an ancient settlement dating to the Yayoi period, a period that was significant for the emergence of organized food production, as well as a unique element associated with the culture: the creation of distinctive, keyhole-shaped burial mounds.

However, it wasn’t until 2021, during restoration work with many of the artifacts retrieved from the site, that researchers first noticed something significant that had gone unnoticed decades earlier at the time of the artifact’s discovery: tiny serrations were present on one of its edges.

Further examination with the help of X-ray CT scan imaging confirmed the artifact’s identity as a triangular or “beak-shaped” saw, similar to other discoveries from later periods. At the time of its use, the complete saw would likely have measured up to five times the length of the remaining fragmentary portion.

Another notable feature of the saw is that the tip of the blade is bent, which archaeologists think may indicate that the saw was used for work involving fine crafting of wooden or stone items.

Breaking Earlier Records for Japan’s Oldest Saw

The discovery now overturns the previous oldest artifact of its kind known from the region, which was uncovered from a third-century burial mound in Hyogo Prefecture. That saw’s association with the Kofun Period, which thrived near the end of the third century, made it the oldest known at the time of its discovery.

Although additional studies are required, the team says that confirmation of the age of the Hayashi-Fujishima site’s saw would extend the timescales once again on the earliest use of such technologies by as much as a century.

About 400 million years ago, the population of plants with vein systems for transferring water and nutrients, called vascular land plants, exploded. Soon thereafter, rocks from some continental magmas showed notable shifts in their chemical compositions. Geologists have suggested that these magma changes happened worldwide, but some argue that the data might be biased because some geographic regions have more samples to analyze than others. A new research team recently tested whether these magmatic changes occurred on a global scale, versus in isolated mountain belts or volcanic islands. 

Geologists use the chemistry of rocks formed from magma to understand a magma’s history. In particular, a mineral called zircon that forms from cooling magma preserves chemical clues about where the magma came from and what it interacted with. To test whether magma changes were global or local, the authors needed data ranging from the equator to the poles. Continents have shifted over the past 400 million years, so scientists use the latitude a rock had when it formed, called its paleolatitude, to compare samples from different parts of ancient Earth. To understand magma histories worldwide, the team used publicly available chemical data from zircons in magmatic rocks that formed across a wide spread of paleolatitudes.

Chemical elements with the same number of protons but different numbers of neutrons are called isotopes with different masses. To discern how plants influenced magma, the researchers analyzed 2 different isotope signals preserved in the zircons. The first isotope signal comes from the ratio of the heavy to light oxygen isotopes, which increases when sediment mixes into magma. Scientists refer to this value as δ¹⁸O, pronounced “delta 18-O.” 

The second isotope signal comes from the element hafnium, denoted Hf. Geologists use hafnium to estimate how long ago magmas melted and separated from the mantle. Zircon contains 2 Hf isotopes, one of which is stable and one of which is produced by radioactive decay. Because this decay happens over billions of years, the ratio between the 2 Hf isotopes over time shifts only slightly. Geologists express these tiny differences using a shorthand called εHf, pronounced “epsilon hafnium,” which shows how much a magma’s Hf signature has changed from Earth’s original mantle. Lower εHf values indicate magmas that incorporated older crustal rock, while higher εHf values reflect mantle sources.

The researchers found that δ¹⁸O values increased as εHf values decreased in these zircons. They concluded that this trend indicates increasing amounts of land-derived sediment in magmas, corresponding with the evolution of land plants. They suggested that land plants altered the ancient landscape, changing how sediments weathered and moved over land. 

To explore this pattern in detail, the team focused on the Andes Mountains, a region that preserves a long history of magmatic activity across a long span of space and time. Using a database, they accessed isotope data from zircon samples collected in the Andes Mountains by dozens of other research groups. These samples covered 32 degrees of modern latitude and 520 million years of Earth’s history, offering a broad window into how magma chemistry changed during that time.

They found that zircons older than 450 million years had no relationship between their εHf and δ¹⁸O values. However, in zircons younger than 450 million years, δ¹⁸O increased as εHf decreased. The researchers saw this pattern in magmas that formed along the edge of the continent, where one tectonic plate sinks below the other, called a subduction zone. They also saw this pattern in magmas that formed inland, away from the subduction zone, around 200 million years ago during the breakup of the supercontinent Pangaea.

 They found similar results in published zircon isotope data from igneous rocks in China, the Caribbean, Antarctica, Madagascar, and Tasmania. Zircons from each region showed the same relationship as zircons in the Andes. Since paleolatitude can also reflect ancient climate, the researchers compared the ratio of εHf and δ¹⁸O, written as εHf/δ¹⁸O, with paleolatitude to test whether ancient climate zones influenced magma chemistry. They found no link between paleolatitude and εHf/δ¹⁸O. 

With these results in mind, the researchers concluded that the relationship between εHf and δ¹⁸O shifted worldwide after vascular land plants evolved. They argued that as plants spread across the continents, their roots accelerated the breakdown of rocks. This accelerated weathering produced large amounts of sediment that washed into ocean basins and was eventually subducted into the mantle, forever changing the chemistry of magma formed there. They suggested that this chain of events illustrates how life on Earth’s surface can drive changes deep within the planet. 

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