Mitochondrial move-in: Could relocating proteins help diagnose Alzheimer’s?

Background: Mitochondria do far more than just act as “powerhouses”—they are also response hubs that send and receive messages to regulate cellular activity. One way that mitochondria send messages is by generating “mitochondrial reactive oxygen species” (mtROS). Normal mtROS signaling orchestrates many essential cellular and tissue functions, from immune responses to brain function. But if mtROS accumulate in excess, they can cause metabolic dysfunction, inflammation, and aging- or disease-associated pathologies.

New findings: In a recent study, Salk Institute researchers, led by Professor Gerald Shadel and postdoctoral researcher Pau Esparza-Moltó, surveyed human embryonic kidney cells and skin biopsy-derived fibroblasts from Alzheimer’s patients to identify proteins that moved into or out of mitochondria in response to changing mtROS levels.

The findings, published in Redox Biology on August 5, 2025, found many new mtROS-sensitive proteins that changed their cellular home address—with one particular subset called glycolytic enzymes that moved toward and even inside mitochondria. The relocation of glycolytic enzymes to mitochondria could adjust cellular metabolism, protect against cell death, or provide novel functions that allow cells to respond to mitochondrial stress.

Why this is important: The researchers say these glycolytic enzymes could one day serve as biomarkers to screen for in skin biopsies, simplifying diagnosis and assessment of Alzheimer’s disease.

Other authors: Arvind Goswami, Laura Newman, Alexandra Moyzis, Gladys Rojas, Deann Guan, Jeffrey Jones, and Fred Gage of Salk, and Süleyman Bozkurt and Christian Münch of Goethe University.

Funding: The work was supported by the American Heart Assocation-Allen Initiative in Brain Health and Cognitive Impairment award (American Heart Association and The Paul G. Allen Frontiers Group: 19PABH134610000AHA), Fundación Alfonso Martín Escudero (Spain), Spruance Foundation II, George E. Hewitt Foundation for Medical Research, National Institutes of Health (K99GM141482, 1K99AG078557-01A1, RF1 AG056306, R37 AG072502-03), German Research Foundation (project ID 456687919, SFB1531 stromavascular damage control), Cancer Research Institute (Irvington Postdoctoral Fellowship CRI4122 and T32CA009370-39), Salk Audrey Geisel Chair of Biomedical Science, JPB Foundation, and Milky Way Research Foundation.

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