Clever-1 blockade disrupts lipid metabolism and mitochondrial fitness in acute myeloid leukemia

Verdict. Here we identify Clever-1 as a regulator of mitochondrial integrity and lipid-dependent oxidative metabolism in AML. It intersects mitochondrial stress/dysfunction themes (mitochondrial dysfunction; functional impairment; bioenergetics).

What the authors report

Therapy resistance in acute myeloid leukemia (AML) is linked to metabolic plasticity and mitochondrial fitness of leukemic stem and progenitor cells. Clever-1 is a scavenger receptor with established immunoregulatory functions, but its leukemia cell-intrinsic roles remain unclear.

Key results stated in the abstract include the following. Here we identify Clever-1 as a regulator of mitochondrial integrity and lipid-dependent oxidative metabolism in AML. Using the anti—Clever-1 antibody bexmarilimab, we show that Clever-1 inhibition induces early mitochondrial transcriptional reprogramming, followed by suppression of oxidative phosphorylation (OXPHOS) in AML cell lines. Immunoelectron microscopy demonstrates mitochondrial localization of Clever-1, while proteomic analyses reveal altered association with mitochondrial-linked proteins, including ATAD3.

Why it matters for mitochondrial biology

Within mitochondrial research, this work maps primarily to OXPHOS, redox biology, metabolism, therapeutics. It is relevant to mitochondrial dysfunction discourse because the abstract invokes mitochondrial dysfunction, functional impairment, bioenergetics, OXPHOS / ETC. That does not by itself establish a validated disease mechanism; it indicates thematic proximity. Because a therapeutic or interventional angle is present, the piece is of interest for mitochondrial-targeted drug hypothesis generation—subject to full-text validation of endpoints and safety context. OXPHOS/ETC involvement, if confirmed, would place the work in the core of bioenergetic pathophysiology rather than peripheral organelle biology. Server: biorxiv. Posted 2026-08-12. Synthesis confidence is bounded by abstract completeness.

Study design (abstract-level)

Using the anti—Clever-1 antibody bexmarilimab, we show that Clever-1 inhibition induces early mitochondrial transcriptional reprogramming, followed by suppression of oxidative phosphorylation (OXPHOS) in AML cell lines. AML models with high baseline OXPHOS activity are particularly sensitive to Clever-1 inhibition, with mitochondrial dysfunction exacerbated under lipid-restricted or metabolically stressful conditions.

Principal findings

1. Here we identify Clever-1 as a regulator of mitochondrial integrity and lipid-dependent oxidative metabolism in AML.
2. Using the anti—Clever-1 antibody bexmarilimab, we show that Clever-1 inhibition induces early mitochondrial transcriptional reprogramming, followed by suppression of oxidative phosphorylation (OXPHOS) in AML cell lines.
3. Immunoelectron microscopy demonstrates mitochondrial localization of Clever-1, while proteomic analyses reveal altered association with mitochondrial-linked proteins, including ATAD3.
4. Functionally, Clever-1 inhibition reduces mitochondrial delivery of lipoprotein-derived lipids, resulting in selective changes in mitochondrial lipid composition.
5. These changes are accompanied by impaired respiratory complex IV assembly, disrupted cristae architecture, accumulation of dysfunctional mitochondria, and reduced spare respiratory capacity.

Limitations of this brief

• This Mitos brief is an abstract-level synthesis of a preprint; it is not peer review and not a substitute for reading the full paper.
• Preprint status: findings may change with revision or journal review.
• Effect sizes, n numbers, statistics, and full experimental controls are typically incomplete at abstract resolution.
• Primary source: biorxiv DOI 10.64898/2026.08.12.744345 (posted 2026-08-12).

Open scientific questions

• Which specific experimental panels in the full paper establish the strongest causal claim, and how robust are the controls?
• Are OXPHOS defects primary drivers or secondary consequences of broader cellular stress?
• What dose, timing, and off-target profile would be required to take the intervention seriously as a therapeutic hypothesis?
• How do these findings sit relative to prior literature on the same pathway—replication, contradiction, or incremental extension?

Bottom line

For mitochondrial biologists focused on OXPHOS, redox biology, metabolism, this preprint is worth full-text review soon. Abstract-level takeaway: Here we identify Clever-1 as a regulator of mitochondrial integrity and lipid-dependent oxidative metabolism in AML. Confirm methods, effect sizes, and controls in the full PDF before citing the result as established.

Bibliographic record

Abstract-based editorial synthesis by Mitos. Not peer review.