# The CDO1–ACSM3 Axis Mediates Renal Tubule Lipid Deposition and Injury by Causing Mitochondrial Dysfunction in Lupus Nephritis

## TL;DR

The study identifies a new mechanism involving CDO1 and ACSM3 that causes kidney damage in lupus nephritis by disrupting mitochondrial function and lipid buildup.

## Contribution

The novel contribution is the discovery of the CDO1–ACSM3 axis as a mediator of renal tubule injury through mitochondrial dysfunction in lupus nephritis.

## Key findings

- CDO1 downregulates ACSM3, leading to mitochondrial dysfunction and lipid deposition in renal tubules.
- ACSM3 deficiency causes mitochondrial abnormalities and worsens kidney injury in lupus nephritis.
- CDO1 and ACSM3 are potential therapeutic targets for treating lupus nephritis.

## Abstract

What are the main findings?
In Lupus nephritis, CDO1 downregulated ACSM3 expression, leading to mitochondrial morphology disorder and dysfunction, which in turn mediates renal tubular lipid deposition and injury.

In Lupus nephritis, CDO1 downregulated ACSM3 expression, leading to mitochondrial morphology disorder and dysfunction, which in turn mediates renal tubular lipid deposition and injury.

What is the implication of the main finding?
CDO1 and ACSM3 are potential therapeutic targets for lupus nephritis.

CDO1 and ACSM3 are potential therapeutic targets for lupus nephritis.

Renal tubular injury plays a critical role in the progression of lupus nephritis (LN); however, the underlying mechanisms remain poorly understood. In this study, we found that CDO1 expression was significantly positively correlated with the degree of renal tubular injury in renal tissues from LN patients. Using in vitro HK-2 and TCMK-1 cells as well as an in vivo MRL/lpr mouse model, we confirmed that knockdown of CDO1 alleviated renal tubular epithelial cell injury and lipid deposition. Mechanistic studies revealed that CDO1 inhibits lipid metabolism by negatively regulating the expression of ACSM3; notably, downregulation of ACSM3 reversed the ameliorative effects of CDO1 knockdown on lipid deposition and cellular injury. Further investigation demonstrated that ACSM3 deficiency mediates lipid deposition by inducing mitochondrial morphological abnormalities and dysfunction. In summary, this study uncovers a novel mechanism by which the CDO1–ACSM3 axis mediates renal tubular lipid deposition and injury in LN through the regulation of mitochondrial function, offering a potential therapeutic target for this disease.