Thomas G. McWilliams
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View article: Bi-allelic <i>ATG12</i> variants impair autophagy and cause a neurodevelopmental disorder
Bi-allelic <i>ATG12</i> variants impair autophagy and cause a neurodevelopmental disorder Open
Macroautophagy/autophagy is an essential developmental and homeostatic process, defined by the endolysosomal degradation of intracellular components and pathogens. Dysfunctional autophagy is implicated in complex human disease, yet reports…
View article: PDK4 and nutrient responses explain muscle specific manifestation in mitochondrial disease
PDK4 and nutrient responses explain muscle specific manifestation in mitochondrial disease Open
Background Mitochondria elicit various metabolic stress responses, the roles of which in diseases are poorly understood. Here, we explore how different muscles of one individual—extraocular muscles (EOMs) and quadriceps femoris (QFs) muscl…
View article: Dynamic mitophagy trajectories hallmark brain aging
Dynamic mitophagy trajectories hallmark brain aging Open
Studies using mitophagy reporter mice have established steady-state landscapes of mitochondrial destruction in mammalian tissues, sparking intense interest in basal mitophagy. Yet how basal mitophagy is modified by healthy aging in diverse…
View article: Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging
Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging Open
Mitophagy neutralizes mitochondrial damage, thereby preventing cellular dysfunction and apoptosis. Defects in mitophagy have been strongly implicated in age-related neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. W…
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View article: Cultured lymphocytes’ mitochondrial genome integrity is not altered by cladribine
Cultured lymphocytes’ mitochondrial genome integrity is not altered by cladribine Open
Cladribine tablets are a treatment for multiple sclerosis with effects on lymphocytes, yet its mode of action has not been fully established. Here, we analyzed the effects of cladribine on mitochondrial DNA integrity in lymphocytes. We tre…
View article: Cell scientist to watch – Thomas McWilliams
Cell scientist to watch – Thomas McWilliams Open
Thomas McWilliams is Associate Professor of Mitochondrial Medicine at the University of Helsinki, Finland. After completing his undergraduate degree in biochemistry in Ireland, Tom moved to the UK for his PhD in integrative neuroscience at…
View article: Lymphocyte mitochondrial genome integrity is not altered by cladribine
Lymphocyte mitochondrial genome integrity is not altered by cladribine Open
Cladribine tablets are a treatment for multiple sclerosis (MS) with effects on lymphocytes’, yet its mode of action has not been fully established. Here, we evaluated the effects of cladribine on mitochondrial DNA integrity in human lympho…
View article: Fine-tune TMEM11 to unleash basal mitophagy
Fine-tune TMEM11 to unleash basal mitophagy Open
When mitochondrial damage threatens to disrupt cell and tissue homeostasis, selective autophagy (mitophagy) provides an important route to neutralize dysfunctional organelles. Whilst we understand much about stress-induced mitophagy, stead…
View article: Mitochondrial signalling and homeostasis: from cell biology to neurological disease
Mitochondrial signalling and homeostasis: from cell biology to neurological disease Open
Efforts to understand how mitochondrial dysfunction contributes to neurodegeneration have primarily focussed on the role of mitochondria in neuronal energy metabolism. However, progress in understanding the etiological nature of emerging m…
View article: Mitophagy in the aging nervous system
Mitophagy in the aging nervous system Open
Aging is characterised by the progressive accumulation of cellular dysfunction, stress, and inflammation. A large body of evidence implicates mitochondrial dysfunction as a cause or consequence of age-related diseases including metabolic d…
View article: Lipid droplets promote efficient mitophagy
Lipid droplets promote efficient mitophagy Open
Mitophagy neutralizes defective mitochondria via lysosomal elimination. Increased levels of mitophagy hallmark metabolic transitions and are induced by iron depletion, yet its metabolic basis has not been studied in-depth. How mitop…
View article: DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion
DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion Open
View article: Mosaic dysfunction of mitophagy in mitochondrial muscle disease
Mosaic dysfunction of mitophagy in mitochondrial muscle disease Open
View article: Emerging roles of ATG7 in human health and disease
Emerging roles of ATG7 in human health and disease Open
View article: Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids
Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids Open
Background Despite the success of immune checkpoint inhibitors against PD-L1 in the clinic, only a fraction of patients benefit from such therapy. A theoretical strategy to increase efficacy would be to arm such antibodies with Fc-mediated…
View article: ATG7 safeguards human neural integrity
ATG7 safeguards human neural integrity Open
ATG7 drives macroautophagy, hereafter "autophagy", by generating ATG12-ATG5 conjugates and lipidating Atg8 homologs including LC3. A pioneering body of work has defined the requirement of ATG7 for survival in mice and shown that neural-spe…
View article: Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans
Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans Open
We identified several patients with a neurodevelopmental disorder who have survived with a severe loss or complete absence of ATG7, an essential effector enzyme for autophagy without a known functional paralogue. (Funded by the Wellcome Ce…
View article: Comment on “mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than <i>mito</i>-QC”
Comment on “mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than <i>mito</i>-QC” Open
One aspect of selective autophagy that has garnered intense interest is mitochondrial autophagy (mitophagy), particularly PINK1-PRKN-mediated mitophagy as this has direct implications for Parkinson...
View article: Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice
Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice Open
O-GlcNAcylation is an abundant post-translational modification in the nervous system, linked to both neurodevelopmental and neurodegenerative disease. However, the mechanistic links between these phenotypes and site-specific O-GlcNAcylatio…
View article: Autophagy in the mammalian nervous system: a primer for neuroscientists
Autophagy in the mammalian nervous system: a primer for neuroscientists Open
Autophagy refers to the lysosomal degradation of damaged or superfluous components and is essential for metabolic plasticity and tissue integrity. This evolutionarily conserved process is particularly vital to mammalian post-mitotic cells …
View article: A comparative map of macroautophagy and mitophagy in the vertebrate eye
A comparative map of macroautophagy and mitophagy in the vertebrate eye Open
Photoreception is pivotal to our experience and perception of the natural world; hence the eye is of prime importance for most vertebrate animals to sense light. Central to visual health is mitochondrial homeostasis, and the selective auto…
View article: Mitochondrial DNA can be inherited from fathers, not just mothers
Mitochondrial DNA can be inherited from fathers, not just mothers Open
View article: CD40 forward signaling is a physiological regulator of early sensory axon growth
CD40 forward signaling is a physiological regulator of early sensory axon growth Open
Multiple members of the tumor necrosis factor superfamily (TNFSF) regulate the growth and branching of neural processes late in development when neurons are establishing and refining connections. Here we present the first evidence that a T…
View article: A comparative map of macroautophagy and mitophagy in the vertebrate eye
A comparative map of macroautophagy and mitophagy in the vertebrate eye Open
Photoreception is pivotal to our experience and perception of the natural world; hence the eye is of prime importance for most vertebrate animals to sense light. Central to visual health is mitochondrial homeostasis, and the selective auto…
View article: PGC-1β modulates statin-associated myotoxicity in mice
PGC-1β modulates statin-associated myotoxicity in mice Open
View article: Phosphorylation of Parkin at serine 65 is essential for its activation<i>in vivo</i>
Phosphorylation of Parkin at serine 65 is essential for its activation<i>in vivo</i> Open
Mutations in PINK1 and Parkin result in autosomal recessive Parkinson's disease (PD). Cell culture and in vitro studies have elaborated the PINK1-dependent regulation of Parkin and defined how this dyad orchestrates the elimination of dama…
View article: Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand
Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand Open
Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of basal…
View article: Supplementary Table 2 from Phosphorylation of Parkin at serine 65 is essential for its activation <i>in vivo</i>
Supplementary Table 2 from Phosphorylation of Parkin at serine 65 is essential for its activation <i>in vivo</i> Open
Mutations in PINK1 and Parkin result in autosomal recessive Parkinson's disease (PD). Cell culture and in vitro studies have elaborated the PINK1-dependent regulation of Parkin and defined how this dyad orchestrates the elimination …
View article: Supplementary material from "Phosphorylation of Parkin at serine 65 is essential for its activation <i>in vivo</i>"
Supplementary material from "Phosphorylation of Parkin at serine 65 is essential for its activation <i>in vivo</i>" Open
Mutations in PINK1 and Parkin result in autosomal recessive Parkinson's disease (PD). Cell culture and in vitro studies have elaborated the PINK1-dependent regulation of Parkin and defined how this dyad orchestrates the elimination …