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Some forms of regulated cell death, such as apoptosis, are precipitated by the activation of cysteine proteases of the caspase family, including caspase 8, 9, and 3. Other caspases, such as caspase 1 and 4, are well known for their pro-inflammatory functions but regulate cell death in a limited number of pathophysiological settings. Accumulating evidence suggests that the most conserved function of mammalian caspases is not to control cell death sensu stricto, but to regulate inflammatory and immune reactions to dying cells and infectious challenges. Here, we review the molecular and cellular mechanisms though which mammalian caspases connect cell-death signaling to the maintenance of organismal homeostasis. [ABSTRACT FROM AUTHOR]

Autophagy constitutes a prominent mechanism through which eukaryotic cells preserve homeostasis in baseline conditions and in response to perturbations of the intracellular or extracellular microenvironment. Autophagic responses can be relatively non-selective or target a specific subcellular compartment. At least in part, this depends on the balance between the availability of autophagic substrates (“offer”) and the cellular need of autophagic products or functions for adaptation (“demand”). Irrespective of cargo specificity, adaptive autophagy relies on a panel of sensors that detect potentially dangerous cues and convert them into signals that are ultimately relayed to the autophagic machinery. Here, we summarize the molecular systems through which specific subcellular compartments—including the nucleus, mitochondria, plasma membrane, reticular apparatus, and cytosol—convert homeostatic perturbations into an increased offer of autophagic substrates or an accrued cellular demand for autophagic products or functions. [ABSTRACT FROM AUTHOR]

Macroautophagy (herein referred to as autophagy) is an evolutionarily conserved mechanism of adaptation to adverse microenvironmental conditions, including limited nutrient supplies. Several sensors interacting with the autophagic machinery have evolved to detect fluctuations in key metabolic parameters. The signal transduction cascades operating downstream of these sensors are highly interconnected to control a spatially and chronologically coordinated autophagic response that maintains the health and function of individual cells while preserving organismal homeostasis. Here, we discuss the physiological regulation of autophagy by metabolic circuitries, as well as alterations of such control in disease. [ABSTRACT FROM AUTHOR]

Summary Autophagic responses specific for damaged or superfluous mitochondria are crucial for the maintenance of cellular and organismal homeostasis. Recent data demonstrate that components of the inner mitochondrial membrane that are unmasked upon outer membrane permeabilization facilitate the autophagic destruction of the organelle. [ABSTRACT FROM AUTHOR]