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Structure of human PINK1 at a mitochondrial TOM-VDAC array

6 months ago
Mutations in the ubiquitin kinase PINK1 cause early onset Parkinson's Disease, but how PINK1 is stabilized at depolarized mitochondrial translocase complexes has remained poorly understood. We determined a 3.1-Å resolution cryo-electron microscopy structure of dimeric human PINK1 stabilized at an endogenous array of mitochondrial TOM and VDAC complexes. Symmetric arrangement of two TOM core complexes around a central VDAC2 dimer is facilitated by TOM5 and TOM20, both of which also bind PINK1...
Sylvie Callegari

Polypharmacy and its association with dementia, Parkinson's disease, and mortality risk in UK adults: a multistate modeling approach

6 months ago
Polypharmacy is common among older adults and has been linked to adverse outcomes such as dementia, Parkinson's disease (PD), and mortality. However, its influence on transitions between these health states remains understudied in large, population-based cohorts. Using data from 361,970 UK Biobank participants aged 50 and older with up to 15 years of follow-up, we examined the association between polypharmacy, defined as the use of five or more medications, and transitions between health states:...
Jordan Weiss

Compressive Forces Induce Epigenetic Activation of Aged Human Dermal Fibroblasts Through ERK Signaling Pathway

6 months ago
Age-related changes in human dermal fibroblasts (HDFs) contribute to impaired wound healing and skin aging. While these changes result in altered mechanotransduction, the epigenetic basis of rejuvenating aging cells remains a significant challenge. This study investigates the effects of compressive forces on nuclear mechanotransduction and epigenetic rejuvenation in aged HDFs. Using a compressive force application model, the activation of HDFs through alpha-smooth muscle actin (ɑ-SMA) is...
Hui Liu

The Mitochondria-Targeted Peptide Therapeutic Elamipretide Improves Cardiac and Skeletal Muscle Function During Aging Without Detectable Changes in Tissue Epigenetic or Transcriptomic Age

6 months ago
Aging-related decreases in cardiac and skeletal muscle function are strongly associated with various comorbidities. Elamipretide (ELAM), a novel mitochondria-targeted peptide, has demonstrated broad therapeutic efficacy in ameliorating disease conditions associated with mitochondrial dysfunction across both clinical and pre-clinical models. Herein, we investigated the impact of 8-week ELAM treatment on pre- and post-measures of C57BL/6J mice frailty, skeletal muscle, and cardiac muscle function,...
Wayne Mitchell