Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity.

Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.

CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias.

Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem cell transcription factor, MECOM, underlies one key driver mechanism in largely incurable AMLs. How MECOM results in such aggressive AML phenotypes remains unknown.

Isobaric Tagging and Data Independent Acquisition as Complementary Strategies for Proteome Profiling on an Orbitrap Astral Mass Spectrometer.

Comprehensive global proteome profiling that is amenable to high throughput processing will broaden our understanding of complex biological systems. Here, we evaluated two leading mass spectrometry techniques, Data Independent Acquisition (DIA) and Tandem Mass Tagging (TMT), for extensive protein abundance profiling. DIA provides label-free quantification with a broad dynamic range, while TMT enables multiplexed analysis using isobaric tags for efficient cross-sample comparisons.

Expanding the Landscape of Aging via Orbitrap Astral Mass Spectrometry and Tandem Mass Tag (TMT) Integration.

Aging results in a progressive decline in physiological function due to the deterioration of essential biological processes, such as transcription and RNA splicing, ultimately increasing mortality risk. Although proteomics is emerging as a powerful tool for elucidating the molecular mechanisms of aging, existing studies are constrained by limited proteome coverage and only observe a narrow range of lifespan. To overcome these limitations, we integrated the Orbitrap Astral Mass Spectrometer with the multiplex tandem mass tag (TMT) technology to profile the proteomes of three brain tissues (cortex, hippocampus, striatum) and kidney in the C57BL/6JN mouse model, achieving quantification of 8,954 to 9,376 proteins per tissue (cumulatively 12,749 across all tissues).

Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity.

Outer mitochondrial membrane (OMM) proteins communicate with the cytosol and other organelles, including the endoplasmic reticulum. This communication is important in thermogenic adipocytes to increase the energy expenditure that controls body temperature and weight. However, the regulatory mechanisms of OMM protein insertion are poorly understood.